1. Insulin is a peptide hormone that regulates blood glucose levels. It is synthesized and secreted by beta cells in the pancreas.
2. Glucagon is a hormone that increases blood glucose levels by stimulating glycogenolysis and gluconeogenesis in the liver. It is synthesized and secreted by alpha cells in the pancreas.
3. Diabetes mellitus is characterized by hyperglycemia and is classified as type 1 caused by lack of insulin production, type 2 caused by insulin resistance and relative lack of insulin, and gestational diabetes during pregnancy.
Insulin is a hormone produced by the pancreas that regulates blood sugar levels. It is composed of two chains of amino acids and functions by promoting the uptake and storage of glucose in the liver, muscle and fat cells. Diabetes occurs when the pancreas produces little or no insulin (Type 1) or the body does not respond properly to insulin (Type 2), resulting in high blood sugar levels. The main types of diabetes are juvenile onset (Type 1) and maturity onset (Type 2) diabetes.
This document discusses insulin and antidiabetic drugs. It begins by describing the pancreatic axis and role of insulin and glucagon in maintaining glucose homeostasis. It then defines diabetes mellitus and describes the main types, Type 1 and Type 2 diabetes. It discusses treatment approaches for both types, including lifestyle changes and various drug classes. The mechanisms and preparations of insulin are outlined in detail. Finally, it reviews common oral antidiabetic drug classes like sulfonylureas, meglitinides, biguanides, thiazolidinediones and alpha-glucosidase inhibitors.
This document discusses insulin and antidiabetic drugs. It begins by describing the pancreatic axis and role of insulin and glucagon in maintaining glucose homeostasis. It then defines diabetes mellitus and describes the main types, Type 1 and Type 2 diabetes. It discusses treatment approaches for both types, including lifestyle changes and various drug classes. The mechanisms and preparations of insulin are outlined in detail. Finally, it reviews common oral antidiabetic drugs like sulfonylureas, meglitinides, biguanides, thiazolidinediones, and alpha-glucosidase inhibitors.
This document summarizes information about diabetes, including its definition, classification, effects of insulin, and treatments. It begins with an overview of diabetes, defining it as a group of metabolic disorders involving hyperglycemia. It then discusses the two main types of diabetes - type 1 characterized by insulin deficiency and type 2 characterized by insulin resistance - and their causes. Subsequent sections provide details on insulin biosynthesis and secretion, its counter-regulation, effects in different tissues, and role in glucose homeostasis. The document concludes by outlining several classes of medications used to treat diabetes, including sulfonylureas, thiazolidinediones, and newer drugs that target incretin hormones.
1. The document discusses insulin and antidiabetic drugs for treatment of diabetes mellitus. It describes the normal pancreatic axis and role of insulin and glucagon in maintaining glucose homeostasis.
2. It explains the two main types of diabetes - Type 1 characterized by lack of insulin production and Type 2 characterized by insulin resistance. Treatment for Type 1 involves insulin injections while Type 2 focuses on lifestyle changes and oral hypoglycemic drugs.
3. Various insulin preparations are discussed based on their onset, peak time and duration of action. Other antidiabetic drug classes described are sulfonylureas, meglitinides, biguanides, thiazolidinediones and alpha-glucosidase inhibitors.
This document summarizes different types of hypoglycemic agents (drugs used to lower blood sugar) for treating diabetes mellitus. It discusses the main types of diabetes (types 1, 2, 3, and secondary) and classifications of hypoglycemic agents including hormones like insulin, oral hypoglycemic agents like sulfonylureas, biguanides, meglitinides, thiazolidinediones, and alpha-glucosidase inhibitors. For each drug class, it provides details on mechanisms of action, pharmacokinetics, uses, and side effects.
This document summarizes different aspects of diabetes mellitus (DM) and insulin. It defines DM as characterized by elevated blood sugar levels due to lack of insulin. It describes the two main types of DM, and discusses HbA1c levels, insulin secretion, the conversion of proinsulin to insulin, and the storage and metabolic effects of insulin. The document also outlines the mechanisms of insulin action in the liver, muscle, and adipose tissue, describes various insulin preparations and their durations of action, and discusses potential adverse effects and mechanisms to reduce blood sugar levels, including sulfonylureas, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, GLP-1 analogs, and D
Diabetes mellitus (DM):- It is a metabolicdisorder characterized by hyperglycaemia, (fasting plasma glucose ≥ 126 mg/dl and/or ≥ 200 mg/dl 2 hours after 75 g oral glucose),glycosuria, hyperlipidaemia, negative nitrogen balance and sometimes ketonaemia.
Diabetes mellitus, one of the major public health problems worldwide, is a metabolic disorder of multiple etiologies distinguished by a failure of glucose homeostasis with disturbances of carbohydrate, fat and protein metabolism as a result of defects in insulin secretion and/or insulin action.
According to International Diabetes Federation (IDF) report, elevated blood glucose is the third uppermost risk factor for premature mortality, following high blood pressure and tobacco use globally
Cardiovascular diseases, neuropathy, nephropathy, and retinopathy are among the major risks that are associated with diabetes.
These chronic complications may lead to hardening and narrowing of arteries (atherosclerosis) that could advance to stroke, coronary heart disease, and other blood vessel diseases, nerve damage, kidney failure, and blindness with time
Two major types of diabetes mellitus are
1. Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
2. Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
There is β cell destruction in pancreatic islets; majority of cases are autoimmune (type 1A) antibodies that destroy β cells are detectable in blood, but some are idiopathic (type 1B)-no βcell antibody is found.
2.Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disease worldwide.
There is no loss or moderate reduction in β cell mass: insulin in circulation is low. normal or even high. no anti-β -cell antibody is demonstrable: has a high degree of genetic predisposition: generally has a late onset (past middle age). Over 90% cases of diabetes are type 2 DM
Abnormality in gluco-receptor of β cells so that they respond at higher glucose concentration or relative β cell deficiency. In either way. insulin secretion is impaired: may progress to β cells failure.
Reduced sensitivity of peripheral tissues to insulin: reduction in number of insulin receptors, “down regulation” of insulin receptors.
Insulin history:
Insulin was discovered in 1921 by Banting and Best who demonstrated the hypoglycaemic action of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of pancreatic duct.
It was first obtained in pure crystalline form in 1926 and the chemical structure was fully worked out in 1956 by Sanger.
Insulin is a two chain polypeptide having 51 amino acids and MW about 6000.
The A-chain has 21 while B-chain has 30 amino acids.
Insulin is synthesized in the β cells of pancreatic islets as a single chain peptide Preproinsulin (110 AA) from whic
Insulin is a hormone produced by the pancreas that regulates blood sugar levels. It is composed of two chains of amino acids and functions by promoting the uptake and storage of glucose in the liver, muscle and fat cells. Diabetes occurs when the pancreas produces little or no insulin (Type 1) or the body does not respond properly to insulin (Type 2), resulting in high blood sugar levels. The main types of diabetes are juvenile onset (Type 1) and maturity onset (Type 2) diabetes.
This document discusses insulin and antidiabetic drugs. It begins by describing the pancreatic axis and role of insulin and glucagon in maintaining glucose homeostasis. It then defines diabetes mellitus and describes the main types, Type 1 and Type 2 diabetes. It discusses treatment approaches for both types, including lifestyle changes and various drug classes. The mechanisms and preparations of insulin are outlined in detail. Finally, it reviews common oral antidiabetic drug classes like sulfonylureas, meglitinides, biguanides, thiazolidinediones and alpha-glucosidase inhibitors.
This document discusses insulin and antidiabetic drugs. It begins by describing the pancreatic axis and role of insulin and glucagon in maintaining glucose homeostasis. It then defines diabetes mellitus and describes the main types, Type 1 and Type 2 diabetes. It discusses treatment approaches for both types, including lifestyle changes and various drug classes. The mechanisms and preparations of insulin are outlined in detail. Finally, it reviews common oral antidiabetic drugs like sulfonylureas, meglitinides, biguanides, thiazolidinediones, and alpha-glucosidase inhibitors.
This document summarizes information about diabetes, including its definition, classification, effects of insulin, and treatments. It begins with an overview of diabetes, defining it as a group of metabolic disorders involving hyperglycemia. It then discusses the two main types of diabetes - type 1 characterized by insulin deficiency and type 2 characterized by insulin resistance - and their causes. Subsequent sections provide details on insulin biosynthesis and secretion, its counter-regulation, effects in different tissues, and role in glucose homeostasis. The document concludes by outlining several classes of medications used to treat diabetes, including sulfonylureas, thiazolidinediones, and newer drugs that target incretin hormones.
1. The document discusses insulin and antidiabetic drugs for treatment of diabetes mellitus. It describes the normal pancreatic axis and role of insulin and glucagon in maintaining glucose homeostasis.
2. It explains the two main types of diabetes - Type 1 characterized by lack of insulin production and Type 2 characterized by insulin resistance. Treatment for Type 1 involves insulin injections while Type 2 focuses on lifestyle changes and oral hypoglycemic drugs.
3. Various insulin preparations are discussed based on their onset, peak time and duration of action. Other antidiabetic drug classes described are sulfonylureas, meglitinides, biguanides, thiazolidinediones and alpha-glucosidase inhibitors.
This document summarizes different types of hypoglycemic agents (drugs used to lower blood sugar) for treating diabetes mellitus. It discusses the main types of diabetes (types 1, 2, 3, and secondary) and classifications of hypoglycemic agents including hormones like insulin, oral hypoglycemic agents like sulfonylureas, biguanides, meglitinides, thiazolidinediones, and alpha-glucosidase inhibitors. For each drug class, it provides details on mechanisms of action, pharmacokinetics, uses, and side effects.
This document summarizes different aspects of diabetes mellitus (DM) and insulin. It defines DM as characterized by elevated blood sugar levels due to lack of insulin. It describes the two main types of DM, and discusses HbA1c levels, insulin secretion, the conversion of proinsulin to insulin, and the storage and metabolic effects of insulin. The document also outlines the mechanisms of insulin action in the liver, muscle, and adipose tissue, describes various insulin preparations and their durations of action, and discusses potential adverse effects and mechanisms to reduce blood sugar levels, including sulfonylureas, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, GLP-1 analogs, and D
Diabetes mellitus (DM):- It is a metabolicdisorder characterized by hyperglycaemia, (fasting plasma glucose ≥ 126 mg/dl and/or ≥ 200 mg/dl 2 hours after 75 g oral glucose),glycosuria, hyperlipidaemia, negative nitrogen balance and sometimes ketonaemia.
Diabetes mellitus, one of the major public health problems worldwide, is a metabolic disorder of multiple etiologies distinguished by a failure of glucose homeostasis with disturbances of carbohydrate, fat and protein metabolism as a result of defects in insulin secretion and/or insulin action.
According to International Diabetes Federation (IDF) report, elevated blood glucose is the third uppermost risk factor for premature mortality, following high blood pressure and tobacco use globally
Cardiovascular diseases, neuropathy, nephropathy, and retinopathy are among the major risks that are associated with diabetes.
These chronic complications may lead to hardening and narrowing of arteries (atherosclerosis) that could advance to stroke, coronary heart disease, and other blood vessel diseases, nerve damage, kidney failure, and blindness with time
Two major types of diabetes mellitus are
1. Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
2. Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
There is β cell destruction in pancreatic islets; majority of cases are autoimmune (type 1A) antibodies that destroy β cells are detectable in blood, but some are idiopathic (type 1B)-no βcell antibody is found.
2.Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disease worldwide.
There is no loss or moderate reduction in β cell mass: insulin in circulation is low. normal or even high. no anti-β -cell antibody is demonstrable: has a high degree of genetic predisposition: generally has a late onset (past middle age). Over 90% cases of diabetes are type 2 DM
Abnormality in gluco-receptor of β cells so that they respond at higher glucose concentration or relative β cell deficiency. In either way. insulin secretion is impaired: may progress to β cells failure.
Reduced sensitivity of peripheral tissues to insulin: reduction in number of insulin receptors, “down regulation” of insulin receptors.
Insulin history:
Insulin was discovered in 1921 by Banting and Best who demonstrated the hypoglycaemic action of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of pancreatic duct.
It was first obtained in pure crystalline form in 1926 and the chemical structure was fully worked out in 1956 by Sanger.
Insulin is a two chain polypeptide having 51 amino acids and MW about 6000.
The A-chain has 21 while B-chain has 30 amino acids.
Insulin is synthesized in the β cells of pancreatic islets as a single chain peptide Preproinsulin (110 AA) from whic
The document discusses the pancreas and its role in producing both digestive enzymes and peptide hormones like insulin, glucagon, and somatostatin. It focuses on the different types of diabetes, their causes and classifications. Type 1 diabetes results from beta cell destruction leading to absolute insulin deficiency. Type 2 diabetes involves insulin resistance and relative insulin deficiency. Gestational diabetes occurs during pregnancy. The roles and mechanisms of insulin and other hormones in regulating blood glucose levels are described.
Diabetes mellitus (DM):- It is a metabolicdisorder characterized by hyperglycaemia, (fasting plasma glucose ≥ 126 mg/dl and/or ≥ 200 mg/dl 2 hours after 75 g oral glucose),glycosuria, hyperlipidaemia, negative nitrogen balance and sometimes ketonaemia.
Diabetes mellitus, one of the major public health problems worldwide, is a metabolic disorder of multiple etiologies distinguished by a failure of glucose homeostasis with disturbances of carbohydrate, fat and protein metabolism as a result of defects in insulin secretion and/or insulin action.
According to International Diabetes Federation (IDF) report, elevated blood glucose is the third uppermost risk factor for premature mortality, following high blood pressure and tobacco use globally
Cardiovascular diseases, neuropathy, nephropathy, and retinopathy are among the major risks that are associated with diabetes.These chronic complications may lead to hardening and narrowing of arteries (atherosclerosis) that could advance to stroke, coronary heart disease, and other blood vessel diseases, nerve damage, kidney failure, and blindness with time
Two major types of diabetes mellitus are
1. Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
2. Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
There is β cell destruction in pancreatic islets; majority of cases are autoimmune (type 1A) antibodies that destroy β cells are detectable in blood, but some are idiopathic (type 1B)-no βcell antibody is found.
2.Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disease worldwide.
There is no loss or moderate reduction in β cell mass: insulin in circulation is low. normal or even high. no anti-β -cell antibody is demonstrable: has a high degree of genetic predisposition: generally has a late onset (past middle age). Over 90% cases of diabetes are type 2 DM
Abnormality in gluco-receptor of β cells so that they respond at higher glucose concentration or relative β cell deficiency. In either way. insulin secretion is impaired: may progress to β cells failure.
Reduced sensitivity of peripheral tissues to insulin: reduction in number of insulin receptors, “down regulation” of insulin receptors.
Insulin history:
Insulin was discovered in 1921 by Banting and Best who demonstrated the hypoglycaemic action of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of pancreatic duct.
It was first obtained in pure crystalline form in 1926 and the chemical structure was fully worked out in 1956 by Sanger.
Insulin is a two chain polypeptide having 51 amino acids and MW about 6000.
The A-chain has 21 while B-chain has 30 amino acids.
Insulin is synthesized in the β cells of pancreatic islets as a single chain peptide Preproinsulin (110 AA) from which
The pancreas and glucose homeostasis l4princesa_mera
Diabetes mellitus is characterized by elevated blood sugar levels due to a lack of insulin. There are two main types: type 1 involves a failure of insulin production while type 2 involves a gradual deterioration of insulin production. Glycosylated hemoglobin (HbA1c) is used to monitor blood glucose levels over several weeks. Insulin regulates glucose homeostasis by promoting glucose uptake and inhibiting glucose production in the liver and breakdown of fats and proteins. Complications of long-term diabetes include damage to blood vessels leading to issues like retinopathy, nephropathy, and neuropathy. Oral anti-diabetic drugs work by various mechanisms like stimulating insulin release, reducing glucose production, or increasing insulin sensitivity.
Recent advances management of Diabetes Mellitus-Targeting to Gastrointestinal...kiflay mulugeta
This document discusses recent advances in targeting the gastrointestinal tract for diabetes mellitus management. It defines diabetes mellitus and describes two main types. It also discusses incretin hormones like GLP-1 that are released from the gut in response to food. Incretin-based therapies that mimic or protect GLP-1, like GLP-1 agonists and DPP-4 inhibitors, are effective in improving glycemic control and have benefits like weight loss. Bariatric surgery procedures can also help diabetes control by altering gut hormone levels. The document concludes that therapies enhancing GLP-1 signaling are a promising new approach for type 2 diabetes treatment.
Kampala international university Glucagon, insulin & oral hypoglycemic drugs.pptYIKIISAAC
1. The document discusses pancreatic hormones like insulin and glucagon that regulate blood glucose levels.
2. Insulin is released when glucose levels rise and works to lower blood glucose through increasing glucose uptake and metabolism.
3. Glucagon is released when glucose levels fall and works to raise blood glucose through stimulating glycogen breakdown and gluconeogenesis in the liver.
Diabetes mellitus is characterized by hyperglycemia due to insufficient insulin production or ineffective insulin. There are two main types - type 1 diabetes results from autoimmune destruction of insulin-producing pancreatic beta cells, while type 2 diabetes involves insulin resistance along with relative insulin deficiency. Insulin regulates carbohydrate, fat, and protein metabolism, maintaining blood glucose levels. Glucagon has opposing effects, promoting gluconeogenesis and glycolysis to increase glucose levels. Tight regulation of insulin and glucagon secretion is needed to keep glucose within its narrow physiological range.
This document provides an overview of the insulin and glucagon hormones, including their structure, synthesis, regulation of secretion, receptors, and metabolic effects. Insulin is produced in the pancreas and promotes storage and use of glucose, fatty acids, and amino acids in the liver, muscle and fat tissues. Glucagon is also produced in the pancreas and opposes insulin by increasing glucose production and release from the liver during periods of low blood sugar. Disorders of insulin and glucagon action can lead to diabetes mellitus.
Diabetes mellitus (DM):- It is a metabolicdisorder characterized by hyperglycaemia, (fasting plasma glucose ≥ 126 mg/dl and/or ≥ 200 mg/dl 2 hours after 75 g oral glucose),glycosuria, hyperlipidaemia, negative nitrogen balance and sometimes ketonaemia.
Diabetes mellitus, one of the major public health problems worldwide, is a metabolic disorder of multiple etiologies distinguished by a failure of glucose homeostasis with disturbances of carbohydrate, fat and protein metabolism as a result of defects in insulin secretion and/or insulin action.
According to International Diabetes Federation (IDF) report, elevated blood glucose is the third uppermost risk factor for premature mortality, following high blood pressure and tobacco use globally
Cardiovascular diseases, neuropathy, nephropathy, and retinopathy are among the major risks that are associated with diabetes.
These chronic complications may lead to hardening and narrowing of arteries (atherosclerosis) that could advance to stroke, coronary heart disease, and other blood vessel diseases, nerve damage, kidney failure, and blindness with time
Two major types of diabetes mellitus are
1. Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
2. Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
There is β cell destruction in pancreatic islets; majority of cases are autoimmune (type 1A) antibodies that destroy β cells are detectable in blood, but some are idiopathic (type 1B)-no βcell antibody is found.
2.Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disease worldwide.
There is no loss or moderate reduction in β cell mass: insulin in circulation is low. normal or even high. no anti-β -cell antibody is demonstrable: has a high degree of genetic predisposition: generally has a late onset (past middle age). Over 90% cases of diabetes are type 2 DM
Abnormality in gluco-receptor of β cells so that they respond at higher glucose concentration or relative β cell deficiency. In either way. insulin secretion is impaired: may progress to β cells failure.
Reduced sensitivity of peripheral tissues to insulin: reduction in number of insulin receptors, “down regulation” of insulin receptors.
Excess of hyperglycemic hormones (glucagon, ete. ) obesity: ; cause relative insulin deficiency the β cells Tag behind
Insulin history:
Insulin was discovered in 1921 by Banting and Best who demonstrated the hypoglycaemic action of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of pancreatic duct.
It was first obtained in pure crystalline form in 1926 and the chemical structure was fully worked out in 1956 by Sanger.
Insulin is a two chain polypeptide having 51 amino acids and MW about 6000.
The A-chain has 21 while B-chain has 30 amino acids.
Veterinary Pharmacology of Hormone secreted by pancreas Sabal Pokharel
The pancreas secretes several important hormones including insulin, glucagon, somatostatin, and pancreatic polypeptide. The endocrine part of the pancreas contains clusters of cells called islets of Langerhans. The main cell types in the islets are alpha cells which secrete glucagon, beta cells which secrete insulin and amylin, delta cells which secrete somatostatin, and F cells which secrete pancreatic polypeptide. These hormones regulate important metabolic processes like blood glucose levels. Insulin lowers blood glucose while glucagon raises it. Somatostatin inhibits the secretion of insulin and glucagon.
2003 role of incretins in glucose homeostasis and diabetesDr.Mudasir Bashir
The document summarizes key points about incretins, which are hormones that stimulate insulin secretion from the pancreas in response to food intake. It discusses the two main incretins, GIP and GLP-1, including their synthesis, secretion, degradation, effects on insulin and glucagon levels, and role in type 2 diabetes. It also describes potential therapies for type 2 diabetes that aim to enhance the effects of incretins, such as GLP-1 analogs like exenatide, and DPP-4 inhibitors that prevent the breakdown of endogenous GLP-1.
This document discusses diabetes mellitus (DM), including its symptoms, complications if left untreated, and types. It focuses on Type 1 and Type 2 DM. Type 1 is an autoimmune disorder where antibodies destroy insulin-producing beta cells. Type 2 is caused by insulin resistance or insufficient insulin production. The document also covers insulin, its structure and production, mechanism of action, types used to treat DM, and oral hypoglycemic agents including sulfonylureas like tolbutamide.
This document discusses pancreatic hormones and their role in diabetes mellitus. It describes how the pancreas functions as both an exocrine and endocrine gland, secreting digestive enzymes and hormones like insulin and glucagon. Problems with insulin production cause diabetes mellitus, characterized by high blood glucose. The document outlines the roles of insulin and glucagon in regulating blood glucose levels, compares type 1 and type 2 diabetes, and discusses treatment approaches like insulin therapy, oral medications, diet/exercise, and new therapies.
Etiology & pathogenesis of Diabetes MellitusEneutron
This document discusses the etiology, pathogenesis, classification, diagnosis and clinical presentation of diabetes mellitus. It begins with an overview of normal insulin physiology and the mechanisms of insulin secretion. It then covers the classification of diabetes into type 1, type 2 and gestational diabetes based on etiology. The document discusses the pathogenesis of type 1 and type 2 diabetes in detail. It provides criteria for the diagnosis of diabetes, including symptoms and results of fasting plasma glucose, oral glucose tolerance and HbA1c tests. The document concludes with a discussion of laboratory tests used to diagnose and monitor diabetes.
This document discusses various aspects of diabetes and its treatment with insulin and other drugs. It provides details on:
1) The two main types of diabetes - Type 1 characterized by a lack of insulin production and Type 2 characterized by insulin resistance.
2) How insulin controls blood glucose levels via its effects on various tissues like liver, muscle and fat.
3) The different types of insulin preparations used in treatment ranging from short-acting to prolonged-acting insulins.
4) Other oral hypoglycemic drugs used to treat Type 2 diabetes like sulfonylureas and meglitinide analogs which work by stimulating insulin secretion.
Diabetes mellitus is a group of metabolic diseases characterized by high blood glucose levels due to defects in insulin secretion or insulin action. The two main types are type 1 diabetes, caused by destruction of beta cells resulting in insulin deficiency, and type 2 diabetes, caused by insulin resistance and relative insulin deficiency. Chronic hyperglycemia can lead to damage of various organs, especially the eyes, kidneys, nerves, heart and blood vessels. Treatment involves lifestyle management, oral medications or insulin to maintain blood glucose levels as close to normal as possible.
This document summarizes different drugs used for the treatment of diabetes mellitus. It discusses the mechanisms of action, pharmacokinetics and adverse effects of various classes of drugs including insulin, sulfonylureas, meglitinides, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, incretin therapies like DPP-4 inhibitors, SGLT2 inhibitors, amylin analogs, and newer dual PPAR agonists. It also compares standard versus intensive glucose treatment goals and monitoring for diabetes.
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...Donc Test
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The document discusses the pancreas and its role in producing both digestive enzymes and peptide hormones like insulin, glucagon, and somatostatin. It focuses on the different types of diabetes, their causes and classifications. Type 1 diabetes results from beta cell destruction leading to absolute insulin deficiency. Type 2 diabetes involves insulin resistance and relative insulin deficiency. Gestational diabetes occurs during pregnancy. The roles and mechanisms of insulin and other hormones in regulating blood glucose levels are described.
Diabetes mellitus (DM):- It is a metabolicdisorder characterized by hyperglycaemia, (fasting plasma glucose ≥ 126 mg/dl and/or ≥ 200 mg/dl 2 hours after 75 g oral glucose),glycosuria, hyperlipidaemia, negative nitrogen balance and sometimes ketonaemia.
Diabetes mellitus, one of the major public health problems worldwide, is a metabolic disorder of multiple etiologies distinguished by a failure of glucose homeostasis with disturbances of carbohydrate, fat and protein metabolism as a result of defects in insulin secretion and/or insulin action.
According to International Diabetes Federation (IDF) report, elevated blood glucose is the third uppermost risk factor for premature mortality, following high blood pressure and tobacco use globally
Cardiovascular diseases, neuropathy, nephropathy, and retinopathy are among the major risks that are associated with diabetes.These chronic complications may lead to hardening and narrowing of arteries (atherosclerosis) that could advance to stroke, coronary heart disease, and other blood vessel diseases, nerve damage, kidney failure, and blindness with time
Two major types of diabetes mellitus are
1. Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
2. Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
There is β cell destruction in pancreatic islets; majority of cases are autoimmune (type 1A) antibodies that destroy β cells are detectable in blood, but some are idiopathic (type 1B)-no βcell antibody is found.
2.Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disease worldwide.
There is no loss or moderate reduction in β cell mass: insulin in circulation is low. normal or even high. no anti-β -cell antibody is demonstrable: has a high degree of genetic predisposition: generally has a late onset (past middle age). Over 90% cases of diabetes are type 2 DM
Abnormality in gluco-receptor of β cells so that they respond at higher glucose concentration or relative β cell deficiency. In either way. insulin secretion is impaired: may progress to β cells failure.
Reduced sensitivity of peripheral tissues to insulin: reduction in number of insulin receptors, “down regulation” of insulin receptors.
Insulin history:
Insulin was discovered in 1921 by Banting and Best who demonstrated the hypoglycaemic action of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of pancreatic duct.
It was first obtained in pure crystalline form in 1926 and the chemical structure was fully worked out in 1956 by Sanger.
Insulin is a two chain polypeptide having 51 amino acids and MW about 6000.
The A-chain has 21 while B-chain has 30 amino acids.
Insulin is synthesized in the β cells of pancreatic islets as a single chain peptide Preproinsulin (110 AA) from which
The pancreas and glucose homeostasis l4princesa_mera
Diabetes mellitus is characterized by elevated blood sugar levels due to a lack of insulin. There are two main types: type 1 involves a failure of insulin production while type 2 involves a gradual deterioration of insulin production. Glycosylated hemoglobin (HbA1c) is used to monitor blood glucose levels over several weeks. Insulin regulates glucose homeostasis by promoting glucose uptake and inhibiting glucose production in the liver and breakdown of fats and proteins. Complications of long-term diabetes include damage to blood vessels leading to issues like retinopathy, nephropathy, and neuropathy. Oral anti-diabetic drugs work by various mechanisms like stimulating insulin release, reducing glucose production, or increasing insulin sensitivity.
Recent advances management of Diabetes Mellitus-Targeting to Gastrointestinal...kiflay mulugeta
This document discusses recent advances in targeting the gastrointestinal tract for diabetes mellitus management. It defines diabetes mellitus and describes two main types. It also discusses incretin hormones like GLP-1 that are released from the gut in response to food. Incretin-based therapies that mimic or protect GLP-1, like GLP-1 agonists and DPP-4 inhibitors, are effective in improving glycemic control and have benefits like weight loss. Bariatric surgery procedures can also help diabetes control by altering gut hormone levels. The document concludes that therapies enhancing GLP-1 signaling are a promising new approach for type 2 diabetes treatment.
Kampala international university Glucagon, insulin & oral hypoglycemic drugs.pptYIKIISAAC
1. The document discusses pancreatic hormones like insulin and glucagon that regulate blood glucose levels.
2. Insulin is released when glucose levels rise and works to lower blood glucose through increasing glucose uptake and metabolism.
3. Glucagon is released when glucose levels fall and works to raise blood glucose through stimulating glycogen breakdown and gluconeogenesis in the liver.
Diabetes mellitus is characterized by hyperglycemia due to insufficient insulin production or ineffective insulin. There are two main types - type 1 diabetes results from autoimmune destruction of insulin-producing pancreatic beta cells, while type 2 diabetes involves insulin resistance along with relative insulin deficiency. Insulin regulates carbohydrate, fat, and protein metabolism, maintaining blood glucose levels. Glucagon has opposing effects, promoting gluconeogenesis and glycolysis to increase glucose levels. Tight regulation of insulin and glucagon secretion is needed to keep glucose within its narrow physiological range.
This document provides an overview of the insulin and glucagon hormones, including their structure, synthesis, regulation of secretion, receptors, and metabolic effects. Insulin is produced in the pancreas and promotes storage and use of glucose, fatty acids, and amino acids in the liver, muscle and fat tissues. Glucagon is also produced in the pancreas and opposes insulin by increasing glucose production and release from the liver during periods of low blood sugar. Disorders of insulin and glucagon action can lead to diabetes mellitus.
Diabetes mellitus (DM):- It is a metabolicdisorder characterized by hyperglycaemia, (fasting plasma glucose ≥ 126 mg/dl and/or ≥ 200 mg/dl 2 hours after 75 g oral glucose),glycosuria, hyperlipidaemia, negative nitrogen balance and sometimes ketonaemia.
Diabetes mellitus, one of the major public health problems worldwide, is a metabolic disorder of multiple etiologies distinguished by a failure of glucose homeostasis with disturbances of carbohydrate, fat and protein metabolism as a result of defects in insulin secretion and/or insulin action.
According to International Diabetes Federation (IDF) report, elevated blood glucose is the third uppermost risk factor for premature mortality, following high blood pressure and tobacco use globally
Cardiovascular diseases, neuropathy, nephropathy, and retinopathy are among the major risks that are associated with diabetes.
These chronic complications may lead to hardening and narrowing of arteries (atherosclerosis) that could advance to stroke, coronary heart disease, and other blood vessel diseases, nerve damage, kidney failure, and blindness with time
Two major types of diabetes mellitus are
1. Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
2. Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
There is β cell destruction in pancreatic islets; majority of cases are autoimmune (type 1A) antibodies that destroy β cells are detectable in blood, but some are idiopathic (type 1B)-no βcell antibody is found.
2.Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disease worldwide.
There is no loss or moderate reduction in β cell mass: insulin in circulation is low. normal or even high. no anti-β -cell antibody is demonstrable: has a high degree of genetic predisposition: generally has a late onset (past middle age). Over 90% cases of diabetes are type 2 DM
Abnormality in gluco-receptor of β cells so that they respond at higher glucose concentration or relative β cell deficiency. In either way. insulin secretion is impaired: may progress to β cells failure.
Reduced sensitivity of peripheral tissues to insulin: reduction in number of insulin receptors, “down regulation” of insulin receptors.
Excess of hyperglycemic hormones (glucagon, ete. ) obesity: ; cause relative insulin deficiency the β cells Tag behind
Insulin history:
Insulin was discovered in 1921 by Banting and Best who demonstrated the hypoglycaemic action of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of pancreatic duct.
It was first obtained in pure crystalline form in 1926 and the chemical structure was fully worked out in 1956 by Sanger.
Insulin is a two chain polypeptide having 51 amino acids and MW about 6000.
The A-chain has 21 while B-chain has 30 amino acids.
Veterinary Pharmacology of Hormone secreted by pancreas Sabal Pokharel
The pancreas secretes several important hormones including insulin, glucagon, somatostatin, and pancreatic polypeptide. The endocrine part of the pancreas contains clusters of cells called islets of Langerhans. The main cell types in the islets are alpha cells which secrete glucagon, beta cells which secrete insulin and amylin, delta cells which secrete somatostatin, and F cells which secrete pancreatic polypeptide. These hormones regulate important metabolic processes like blood glucose levels. Insulin lowers blood glucose while glucagon raises it. Somatostatin inhibits the secretion of insulin and glucagon.
2003 role of incretins in glucose homeostasis and diabetesDr.Mudasir Bashir
The document summarizes key points about incretins, which are hormones that stimulate insulin secretion from the pancreas in response to food intake. It discusses the two main incretins, GIP and GLP-1, including their synthesis, secretion, degradation, effects on insulin and glucagon levels, and role in type 2 diabetes. It also describes potential therapies for type 2 diabetes that aim to enhance the effects of incretins, such as GLP-1 analogs like exenatide, and DPP-4 inhibitors that prevent the breakdown of endogenous GLP-1.
This document discusses diabetes mellitus (DM), including its symptoms, complications if left untreated, and types. It focuses on Type 1 and Type 2 DM. Type 1 is an autoimmune disorder where antibodies destroy insulin-producing beta cells. Type 2 is caused by insulin resistance or insufficient insulin production. The document also covers insulin, its structure and production, mechanism of action, types used to treat DM, and oral hypoglycemic agents including sulfonylureas like tolbutamide.
This document discusses pancreatic hormones and their role in diabetes mellitus. It describes how the pancreas functions as both an exocrine and endocrine gland, secreting digestive enzymes and hormones like insulin and glucagon. Problems with insulin production cause diabetes mellitus, characterized by high blood glucose. The document outlines the roles of insulin and glucagon in regulating blood glucose levels, compares type 1 and type 2 diabetes, and discusses treatment approaches like insulin therapy, oral medications, diet/exercise, and new therapies.
Etiology & pathogenesis of Diabetes MellitusEneutron
This document discusses the etiology, pathogenesis, classification, diagnosis and clinical presentation of diabetes mellitus. It begins with an overview of normal insulin physiology and the mechanisms of insulin secretion. It then covers the classification of diabetes into type 1, type 2 and gestational diabetes based on etiology. The document discusses the pathogenesis of type 1 and type 2 diabetes in detail. It provides criteria for the diagnosis of diabetes, including symptoms and results of fasting plasma glucose, oral glucose tolerance and HbA1c tests. The document concludes with a discussion of laboratory tests used to diagnose and monitor diabetes.
This document discusses various aspects of diabetes and its treatment with insulin and other drugs. It provides details on:
1) The two main types of diabetes - Type 1 characterized by a lack of insulin production and Type 2 characterized by insulin resistance.
2) How insulin controls blood glucose levels via its effects on various tissues like liver, muscle and fat.
3) The different types of insulin preparations used in treatment ranging from short-acting to prolonged-acting insulins.
4) Other oral hypoglycemic drugs used to treat Type 2 diabetes like sulfonylureas and meglitinide analogs which work by stimulating insulin secretion.
Diabetes mellitus is a group of metabolic diseases characterized by high blood glucose levels due to defects in insulin secretion or insulin action. The two main types are type 1 diabetes, caused by destruction of beta cells resulting in insulin deficiency, and type 2 diabetes, caused by insulin resistance and relative insulin deficiency. Chronic hyperglycemia can lead to damage of various organs, especially the eyes, kidneys, nerves, heart and blood vessels. Treatment involves lifestyle management, oral medications or insulin to maintain blood glucose levels as close to normal as possible.
This document summarizes different drugs used for the treatment of diabetes mellitus. It discusses the mechanisms of action, pharmacokinetics and adverse effects of various classes of drugs including insulin, sulfonylureas, meglitinides, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, incretin therapies like DPP-4 inhibitors, SGLT2 inhibitors, amylin analogs, and newer dual PPAR agonists. It also compares standard versus intensive glucose treatment goals and monitoring for diabetes.
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3. INSULIN CHEMISTRY
Insulin is a peptide hormone consisting of 51 amino acids arranged as two
polypeptide chains, an A-chain and B-chain, connected by disulfide bonds;
5. Regulation of insulin secretion
1. Chemical
Glucose entry
↓
Activation of the glucosensor
↓
↓
Inhibits the ATP-sensitive K+ channel
↓
Partial depolarization of the β cells
↓
Intracellular Ca2+ availability
↓
exocytotic release of insulin storing granules
7. 3. Neural:
•Adrenergic α2 receptor activation decreases insulin
release (predominant) by inhibiting β cell adenylyl
cyclase.
•Adrenergic β2 stimulation increases insulin release (less
•Adrenergic β2 stimulation increases insulin release (less
prominent) by stimulating β cell adenylyl cyclase.
•Cholinergic—muscarinic activation by ACh or vagal
stimulation causes insulin secretion.
8. Mechanism of action of Insulin
The insulin receptor is composed of two α and two β-subunits.
↓
Insulin binds to the α-subunit on the extracellular surface of the cell
↓
Phosphorylation of tyrosine residues on cytoplasmic proteins ,termed
the insulin receptor substrate (IRS) 1 and 2.
↓
↓
IRS phosphorylation provides a docking site for other intracellular
signaling proteins.
↓
P85 (regulatory subunit of PI-3 kinase ) becomes activated and
dimerizes with its catalytic subunit (p-110)
↓
This complex mobilizes the translocation of glucose transporters to
the cell membrane surface, which promotes hexose transport.
9.
10. ACTIONS (Rang and Dale)
Insulin is the main hormone controlling intermediary metabolism,
having actions on liver, fat and muscle . It is an anabolic hormone: its
overall effect is to conserve fuel by facilitating the uptake and storage of
glucose, amino acids and fats after a meal.
Liver Insulin influences glucose metabolism in most tissues, especially
the liver, where it inhibits glycogenolysis (glycogen breakdown) and
the liver, where it inhibits glycogenolysis (glycogen breakdown) and
gluconeogenesis (synthesis of glucose from non-carbohydrate sources)
while stimulating glycogen synthesis. It also increases glucose utilisation
(glycolysis), but the overall effect is to increase hepatic glycogen stores.
Muscle In muscle, unlike liver, uptake of glucose is slow and is the rate-
limiting step in carbohydrate metabolism. The main effects of insulin are
to increase facilitated transport of glucose via a transporter called Glut-4,
and to stimulate glycogen synthesis and glycolysis.
11. Adipose tissue Insulin increases glucose uptake by Glut-4 in adipose
tissue as well as in muscle, enhancing glucose metabolism. One of the main
end products of glucose metabolism in adipose tissue is glycerol, which is
esterified with fatty acids to form triglycerides, thereby affecting fat
metabolism. Insulin increases synthesis of fatty acid and triglyceride in
adipose tissue and in liver. It inhibits lipolysis, partly via
dephosphorylation—and hence inactivation—of lipases . It also inhibits the
lipolytic actions of adrenaline, growth hormone and glucagon by opposing
their actions on adenylyl cyclase.
their actions on adenylyl cyclase.
Insulin stimulates uptake of amino acids into muscle and increases protein
synthesis. It also decreases protein catabolism and inhibits oxidation of
amino acids in the liver.
13. Long-term effects of insulin In addition to its rapid effects on
metabolism, exerted via altered activity of enzymes and transport
proteins, insulin has long-term actions via altered enzyme synthesis. It is
an important anabolic hormone during fetal development. It stimulates
cell proliferation and is implicated in somatic and visceral growth and
development.
14. DISTRIBUTION AND DEGRADATION OF INSULIN
Insulin circulates in blood as a monomer, and its volume of distribution
approximates the volume of extracellular fluid. Under fasting conditions, the
pancreas secretes about 40 µg (1 unit) of insulin/h into the portal vein to achieve
a concentration of insulin in portal blood of 2–4 ng/mL (50–100 µunits/mL) and
in the peripheral circulation of 0.5 ng/mL (12 µunits/mL) or ~0.1 nM. After
ingestion of a meal, there is a rapid rise in the concentration of insulin in portal
blood, followed by a parallel but smaller rise in the peripheral circulation.
The plasma t1/2 of insulin normally is ~5–6 minutes but may be increased in
The plasma t1/2 of insulin normally is ~5–6 minutes but may be increased in
diabetics who develop anti-insulin antibodies. The t1/2 of proinsulin is longer
than that of insulin.
Degradation of insulin occurs primarily in liver, kidney, and muscle. About 50%
of the insulin that reaches the liver via the portal vein is destroyed and never
reaches the general circulation.
Insulin is filtered by the renal glomeruli and is reabsorbed by the tubules, which
also degrade it. Severe impairment of renal function affects insulin clearance to a
greater extent than does hepatic disease.
15. GLUCAGON
Glucagon is a single-chain
polypeptide of 21 amino acid
residues synthesized mainly in the α
cell of the islets, but also in the upper
gastrointestinal tract. It has
gastrointestinal tract. It has
considerable structural homology
with other gastrointestinal tract
hormones, including secretin,
vasoactive intestinal peptide and GIP.
16. Regulation of Glucagon secretion:
• Physiological stimuli to glucagon secretion is the concentration of
amino acids, in particular L-arginine, in plasma.
• Sympathetic nerve activity and circulating adrenaline stimulate
glucagon release via β-adrenoceptors.
Clinical uses of Glucagon:
Clinical uses of Glucagon:
• Treatment of hypoglycaemia in unconscious patients
• Treatment of acute cardiac failure precipitated by β -
adrenoceptor antagonists.
17. Mechanism of Glucagon:
It acts on specific G-protein-coupled receptors to stimulate
adenylyl cyclase, and consequently its actions are somewhat similar
to β-adrenoceptor mediated actions of adrenaline.
18. Incretin
Gut hormone which under physiological circumstances stimulates or contribute
s to the stimulation of the secretion of pancreatic hormones [insulin, glucagon,
PP (pancreatic polypeptide), and pancreatic somatostatin] is an incretin.
• Glucagon-like peptide (GLP)-1
• Glucose-dependent insulinotropic polypeptide (GIP)
S197.full.pdf (diabetesjournals.org)
19. GIP:
GIP is a peptide of 42 amino acids belonging to the glucagon-secretin family
of peptides, the members of which have pronounced sequence homology,
particularly in the NH2-terminus.
GIP receptors are expressed in the islets and also in the gut, adipose tissue,
heart, pituitary, adrenal cortex, and several regions of the brain .
GIP is secreted from specific endocrine cells, so-called K cells, with highest
density in the duodenum but found in the entire small intestinal mucosa.
density in the duodenum but found in the entire small intestinal mucosa.
Secretion is stimulated by absorbable carbohydrates and by lipids.
GIP secretion is therefore greatly increased in response to meals, resulting in
10- to 20-fold elevations of the plasma concentration .
Interaction of GIP with its receptor on the β-cells causes elevation of cAMP
levels, which in turn increases the intracellular calcium concentration and
enhances exocytosis of insulin-containing granules by a mechanism distal to
the elevation of calcium.
20. GLP-1.
GLP-1 is a product of the glucagon gene. It is expressed not only in pancreat
ic α-cells but also in the L-cells of the intestinal mucosa, one of the m
ost abundant endocrine cells of the gut . GLP-1 secretion is stimulated by th
e presence of nutrients in the lumen of the gut.
GLP-1 is one of the most potent insulin-releasing substances known, exceed
GLP-1 is one of the most potent insulin-releasing substances known, exceed
ing that of GIP . Like GIP it interacts with a G protein–coupled receptor on
the β-cells, which causes accumulation of cAMP.
21. Diabetes Mellitus:
Diabetes mellitus is a group of metabolic diseases characterized by
hyperglycemia resulting from defects in insulin secretion, insulin
action, or both. The chronic hyperglycemia of diabetes is associated
with long-term damage, dysfunction, and failure of various organs,
especially the eyes, kidneys, nerves, heart, and blood vessels..
Classifications of diabetes:
•Type 1 diabetes (formerly insulin-dependent diabetes mellitus),
•Type 2 diabetes (formerly non insulin dependent diabetes mellitus),
•Gestational diabetes, and
•Diabetes due to other causes (e.g., genetic defects or medication
induced
22. Type 1 diabetes or insulin-dependent diabetes
mellitus
Onset: Most commonly afflicts individuals in puberty or early adulthood,
but some latent forms can occur later in life.
Causes: Loss of β -cell function is usually ascribed to autoimmune
mediated processes directed against the β-cell, and it may be triggered by an
invasion of viruses or the action of chemical toxins.
Symptoms: Classical symptoms (3 Ps)
• Polydipsia,
• Polyphagia
• Polyuria
• Weight loss
23. Idiopathic diabetes.
Some forms of type 1 diabetes have no known etiologies. Some of
these patients have permanent insulinopenia (insulinopenic-
Relating to a form of diabetes mellitus that results from an
inadequate secretion of insulin.) and are prone to ketoacidosis, but
inadequate secretion of insulin.) and are prone to ketoacidosis, but
have no evidence of autoimmunity.
24. Diabetic ketoacidosis
(Diabetic coma) Ketoacidosis of different grades generally occurs in insulin
dependent diabetics.
Lack of insulin
↓
Hyperglycemia ↑lipolysis
↓ ↓
Glycosuria ↑FFA
↙ ↘ ↓
loss of electrolyte Formation of ketone body
loss of electrolyte Formation of ketone body
↓ ↓
Loss of water K+ depletion metabolic acedosis
↓ ↓ ↙ ↘
Dehydration (+)chronotropic (+)CTZ hyperventilation
↓ ↓
Hyperosmolarity ↑myocardial contractility
↑HR
↓ ↓
Intracellular dehydration tachycardia
↓
Impairment in the consciousness
25. Type 2 diabetes or insulin-independent diabetes
mellitus
Type 2 diabetes is characterized by tissue resistance to the action of
insulin combined with a relative deficiency in insulin secretion. A given
individual may have more resistance or more beta-cell deficiency, and
the abnormalities may be mild or severe. Although insulin is produced
by the beta cells in these patients, it is inadequate to overcome the
resistance, and the blood glucose rises.
26. Insulin resistance
Several putative sites of insulin resistance have been identified in humans, including
•A defective binding of insulin to a receptor
•A blunting of insulin signal transduction.
•Conditions associated with elevated insulin levels (hyperinsulinism), such as obesity, may be the
result of down-regulation in the number of insulin receptors, effectively resulting in a state of
insulin resistance. Conversely, decreases in insulin levels (e.g., diabetes) may lead to an up-
regulation of the receptors, which may shift the insulin dose–response curve to the left; that is, less
insulin would be required to produce a given biological effect.
insulin would be required to produce a given biological effect.
•Insulin resistance also has been associated with a number of hormonal and metabolic states,
including Cushing’s syndrome (excessive corticosteroids), acromegaly (excessive growth
hormone),and gestational diabetes.
•Physiological or psychological stress also can contribute to insulin resistance.
•Gestational diabetes mellitus is a condition that develops during the second trimester of
pregnancy; the cause may be rises in human placental lactogen and other hormones that
contribute to insulin resistance. This condition usually resolves during the postpartum period.
•Another relatively common form of insulin resistance is often seen in women with polycystic
ovarian syndrome, a disorder that is associated with hyperandrogenism, hirsutism, menstrual
irregularities,obesity,and infertility.
28. Type 4 Diabetes Mellitus
Gestational diabetes (GDM) is defined as any abnormality in glucose levels
noted for the first time during pregnancy. During pregnancy, the placenta
and placental hormones create an insulin resistance that is most
pronounced in the last trimester.
Screening may be deferred in lower-risk women until the 24th to 28th week
of gestation
Risk factors of type 4 DM:
•Older women
•Over wt.
•Family history of diabetes.
•Had previous GDM
•Previous large baby.
•Previous unexplained still birth or neonatal death.
29. Insulin resistance
Several putative sites of insulin resistance have been identified in humans,
including
•A defective binding of insulin to a receptor
•A blunting of insulin signal transduction.
•Conditions associated with elevated insulin levels (hyperinsulinism),
•Insulin resistance also has been associated with a number of hormonal and
metabolic states, including Cushing’s syndrome (excessive corticosteroids),
acromegaly (excessive growth hormone),and gestational diabetes.
•Physiological or psychological stress also can contribute to insulin resistance.
•Gestational diabetes mellitus is a condition that develops during the second
trimester of pregnancy;the cause may be rises in human placental lactogen and
other hormones that contribute to insulin resistance.
• Another relatively common form of insulin resistance is often seen in women
with polycystic ovarian syndrome, a disorder that is associated with
hyperandrogenism, hirsutism, menstrual irregularities,obesity,and infertility.
30. METABOLIC DISTURBANCES AND COMPLICATIONS OF
THE DIABETIC STATE
•Glucosuria
•Protein catabolism
•The catabolism of lipids and fatty acids
•The catabolism of lipids and fatty acids
•Diabetic ketoacidosis
•Diabetes mellitus can cause microvascular complications (e.g.,
retinopathy, nephropathy, and neuropathy) and macrovascular
complications (e.g., atherosclerotic cardiovascular disease)
31. Complications of diabetes mellitus:
1.Microvascular complication:
a. Retinopathy
b. Nephropathy
c. Neuropathy
c. Neuropathy
2. Macrovascular complication:
a. Atherosclerotic cardiovascular disease
32. Symptoms:
•Spots or dark strings floating in your vision (floaters)
•Blurred vision.
•Fluctuating vision.
1. Diabetic retinopathy
•Fluctuating vision.
•Impaired color vision.
•Dark or empty areas in your vision.
•Vision loss.
33. DM (hyperglycemia)
↓
↑basement membrane protein production
↑fibronectin,Collagen, laminine
↓
Basement membrane thickening
Vascular occlusion Vascular cell
death
Diabetic Retinopathy
Retinal hypoxia
↓
Production of pro-inflammatory cytokines and pro-
angiogenic growth factors (VEGF).
↓
Unregulated growth of new blood vessels, increased
vascular permeability
↓
Retinal neovascularization
35. Symptoms of Diabetic Nephropathy:
• Worsening blood pressure control.
• Protein in the urine.
• Swelling of feet, ankles, hands or eyes.
• Increased need to urinate.
• Reduced need for insulin or diabetes medicine.
• Confusion or difficulty concentrating.
• Shortness of breath.
38. Symptoms of Diabetic Neuropathy:
• Numbness or reduced ability to feel pain or temperature
changes
• Tingling or burning sensation
• Sharp pains or cramps
• Sharp pains or cramps
• Increased sensitivity to touch — for some people, even a
bed sheet's weight can be painful
• Serious foot problems, such as ulcers, infections, and
bone and joint pain.
41. Atherosclerotic cardiovascular disease
Risk factors as diverse as
• Dyslipidemia,
• Vasoconstrictor hormones inculpated in hypertension.
• Vasoconstrictor hormones inculpated in hypertension.
• Glycoxidation associated with hyperglycemia.
• Proinflammatory cytokines derived from excess adipose
tissue.
42. Pathophysiology:
In diabetes, LDL cholesterol is the small, dense form and
Can more easily penetrate
↓
More susceptible to oxidation
Once the particles become oxidized they acquire new properties
↓
recognized by the immune system as “foreign”
↓
↓
Abnormal biological responses, such as attracting leukocytes to
the intima of the vessel
↓
leukocytes ingest lipids and differentiate into foam cells
↓
Stimulating the proliferation of leukocytes, endothelial cells,
and smooth muscle cells
↓
Formation of atherosclerotic plaque
43. Diabetes inducing Dyslipidemia
Diabetes
↓
↑free fatty acid delivery to liver
↓
↑TG level and↑APO-B level
↓
↑formation of VLDL
↑formation of VLDL
↓
↑Cholesterol ester transfer protein (CETP) exchange
↓
Production of triglyceride rich HDL and LDL
↓
Hepatic lipase hydrolyses the TG on HDL and LDL
↓
Production of small dense LDL and HDL
↓affinity of APO-A protein for small HDL
dissociation and clearance of APO-A
45. CLINICAL MANAGEMENT OF DIABETES
• Diet is the cornerstone of the management of diabetes.
• Exercise is also an important component in managing diabetes,
particularly in obese individuals with NIDDM.
• Treatment regimens: Calorie restricted diet in combination with
exogenous insulin or oral hypoglycemic drugs..
exogenous insulin or oral hypoglycemic drugs..
• The administration of insulin is required for the treatment of type I
(IDDM) and in cases of type II (NIDDM) that are refractory to
management with oral hypoglycemic drugs.
• Unstable or ketoacidosis prone diabetics are usually require multiple
injections of combinations of short, intermediate, and/or long-
acting insulin preparations .
46. Post Prandial glucose level
The word postprandial means
after a meal; therefore, PPG
concentrations refer to plasma
glucose concentrations after
eating.
47. Glucose tolerance test
A glucose tolerance test is used to determine a person's ability to
handle a glucose load. The test can show whether a person can
metabolize a standardized measured amount of glucose. The results
can be classified as normal, impaired, or abnormal.
Range :
Condition Level (After 2 hour)
Normal less than 140 mg/dL
Impaired 140 to 200 mg/dL
Diagnostic test for Type 1 or type 2 DM greater than 200 mg/dL
Diagnostic test for Gestational Diabetes greater than 140 mg/dL
48. HbA1C
The term HbA1c refers to glycated hemoglobin. It develops when
The term HbA1c refers to glycated hemoglobin. It develops when
haemoglobin, a protein within red blood cells that carries oxygen
throughout the body, joins with glucose in the blood, becoming
‘glycated’.
For people with diabetes this is important as the higher the
HbA1c, the greater the risk of developing diabetes-related
complications.
49. How does HBA1c can give an accurate average measurement of
average blood glucose?
average blood glucose?
The amount of glucose that combines with this protein is directly
proportional to the total amount of sugar that is in the system at that
time.
Because red blood cells survive for 8-12 weeks in the human body before
renewal, measuring glycated haemoglobin (or HbA1c) can be used to
reflect average blood glucose levels over that duration, providing a useful
longer-term gauge of blood glucose control.
50.
51. Hypoglycemia (Low Blood sugar)
When your blood sugar level is less than 70 mg/dL.
Signs and symptoms
•Feeling shaky
•Being nervous or anxious
•Sweating, chills and clamminess
•Irritability or impatience or Confusion
•Fast heartbeat
•Fast heartbeat
•Feeling lightheaded or dizzy
•Nausea
•Feeling weak or having no energy
Treatment - The "15-15 Rule"
The 15-15 rule—have 15 grams of carbohydrate to raise the blood
sugar and check it after 15 minutes. If it’s still below 70 mg/dL, have
another serving.
53. Principal Types and Duration of
Action of Insulin Preparations:
Four principal types of injected insulins are available:
(1) Rapid acting, with very fast onset and short duration
(2) Short-acting, with rapid onset of action;
(3) Intermediate-acting; and
(4) long-acting, with slow onset of action
54. 1. Rapid-acting insulin
Three commercially available injected rapid-acting insulin
analogs—
a. Insulin lispro,
b. Insulin aspart , and
c. Insulin glulisine.
55. Benefit of The rapid-acting insulin
• Permit more physiologic prandial insulin replacement
because their rapid onset.
• Early peak action more closely mimic normal endogenous
prandial insulin secretion than does regular insulin.
• Their duration of action is rarely more than 4–5 hours,
which decreases the risk of late postmeal hypoglycemia.
• Preferred insulins for use in continuous subcutaneous
insulin infusion devices.
56. Insulin lispro:
•The first monomeric insulin analog to be marketed.
•Produced by recombinant technology wherein two amino acids
near the carboxyl terminal of the B chain have been reversed in
position: Proline at position B28 has been moved to B29, and lysine
at position B29 has been moved to B28.
•Lispro insulin displays very similar actions to insulin. When
injected subcutaneously, the drug quickly dissociates into
monomers and is rapidly absorbed .
• Slightly greater reduction in HbA1c compared to regular insulin
has been reported. Fewer hypoglycaemic episodes occurred.
• within 5–15 minutes and peak activity as early as 1 hour. The time
to peak action is relatively constant, regardless of the dose.
57. Insulin aspart
• Created by the substitution of the B28 proline with a
negatively charged aspartic acid.
• Its absorption and activity profile are similar to those of
insulin lispro, and
insulin lispro, and
• It has binding properties, activity, and mitogenicity
characteristics similar to those of regular insulin in addition
to equivalent immunogenicity.
58. Short-acting insulin
Regular insulin
•Short-acting soluble crystalline zinc insulin that is now made by
recombinant DNA techniques to produce a molecule identical to
that of human insulin.
•Onset of action: Its effect appears within 30 minutes, peaks
between 2 and 3 hours after subcutaneous injection, and generally
between 2 and 3 hours after subcutaneous injection, and generally
lasts 5–8 hours.
• In high concentrations, eg, in the vial, regular insulin molecules
self-aggregate to form dimers that stabilize around zinc ions to
create insulin hexamers that causes a delayed onset and prolongs
the time to peak action.
• Regular insulin should be injected 30–45 or more minutes before
the meal to minimize the mismatching.
59. Disadvantage:
• The delayed absorption, dose-dependent duration of action,
and variability of absorption ( 25%) of regular human insulin
frequently results in a mismatching of insulin availability with
need, and its use is declining.
• Short-acting, regular soluble insulin is the only type that should
• Short-acting, regular soluble insulin is the only type that should
be administered intravenously because the dilution causes the
hexameric insulin to immediately dissociate into monomers.
Advantage:
1. Particularly useful for intravenous therapy in the
management of diabetic ketoacidosis
2. when the insulin requirement is changing rapidly, such as
after surgery or during acute infections
60. 3. Intermediate-acting and long-acting insulins
a. NPH (neutral protamine Hagedorn, or isophane) insulin:
• NPH insulin is an intermediate-acting insulin
• Prepared by combining appropriate amounts of insulin and
protamine.
• Onset of action: 2–5 hours and duration of 4–12 hours.
• it is usually mixed with regular, lispro, aspart, or glulisine insulin
and given two to four times daily for insulin replacement.
• The action of NPH is highly unpredictable, and its variability of
absorption is over 50%.
• The clinical use of NPH is declining because of its adverse
pharmacokinetics.
61. b. Insulin glargine:
• Insulin glargine is a soluble, “peakless” long-acting insulin analog.
• The introduction of two positive arginine residues at the carboxy
terminus of the B-chain shifts the isoelectric point of the peptide from
5.4 to 6.7, thus creating a molecule that is soluble at pH 4 but less
soluble at neutral (physiological) pH (in subcutaneous tissue).
soluble at neutral (physiological) pH (in subcutaneous tissue).
• Insulin glargine has a slow onset of action (1–1.5 hours) and achieves
a maximum effect after 4–6 hours. This maximum activity is
maintained for 11–24 hours or longer.
• It has six fold to seven fold greater binding than native insulin to the
insulin-like growth factor-1 (IGF-1) receptor, but the clinical
significance of this is unclear.
62. c. Insulin detemir
• This insulin is the most recently developed long-acting insulin analog.
The terminal threonine is dropped from the B30 position and myristic
acid is attached to the terminal B29 lysine.
• These modifications prolong the availability of the injected analog by
increasing both self-aggregation in subcutaneous tissue and reversible
albumin binding.
• Its use is associated with less hypoglycemia than NPH insulin.
• Insulin detemir has a dose-dependent onset of action of 1–2 hours and
duration of action of more than 12 hours.
63. Case Study 1
George Smith is taking insulin for the first time. His
physician prescribes 20 units NPH and 5 units regular
insulin at breakfast, and 10 units NPH and 5 units regular
insulin at dinner.
insulin at dinner.
After a few days, Mr. Smith begins to notice this approximate
pattern in his blood sugar measurements: 8 A.M. (fasting), about
110; noon (before lunch), about 120; 5 P.M. (before dinner), about
55; bedtime, about 115. When his blood sugar is about 55, he feels
shaky and sweaty, but this goes away if he has something to eat.
64. Which of the following changes would you
recommend to his regimen?
1. Decrease his morning regular insulin
2. Decrease his morning NPH insulin
3. Stop evening insulin and add a sulfonylurea at bedtime
4. Have him eat a larger lunch
5. Move his evening NPH insulin from supper time to
bedtime.
65. Case Study 2
A 19 year old female nursing student of Central Philippine
University was diagnosed with Type I Diabetes Mellitus. She
was 10 years of age when symptoms of the disease was observed.
She experienced severe weight loss and increased urination
especially at night, thus causing her sleep disturbances. For
especially at night, thus causing her sleep disturbances. For
three months, her mother has checked her blood sugar level
regularly, hoping the symptoms would soon recede. But soon
after, the patient consulted a physician.
Diagnosis:
Laboratory tests taken by the patient includes Fasting blood
sugar (FBS) and test for Glycosylated hemoglobin (Hemoglobin
A1c) with the result of 9.5% deviating from the normal range of
4-5.6%.
66. What would you recommend as her
treatment and what's your prognosis
about her case?
67. Insulin Delivery Systems
A. Standard Delivery
The standard mode of insulin therapy is
subcutaneous injection using conventional
disposable needles and syringes.
B. Portable Pen Injectors:
• These contain cartridges of insulin and
replaceable needles.
• These are regular insulin, insulin lispro, insulin
aspart, insulin glulisine, insulin glargine, insulin
detemir, and several mixtures of NPH with
regular, lispro, or aspart insulin .
• They have been well accepted by patients
because they eliminate the need to carry syringes
and bottles of insulin to the workplace and while
traveling.
68. • The devices have a user programmable pump that delivers
individualized basal and bolus insulin replacement doses
Continuous Subcutaneous Insulin
Infusion Devices (CSII, Insulin Pumps)
individualized basal and bolus insulin replacement doses
• Normally, the 24-hour background basal rates are
preprogrammed.
• The traditional pump—which contains an insulin reservoir,
the program chip, the keypad, and the display screen—is about
the size of a pager.
• The abdomen is the favored site for the infusion set.
Insulin aspart, lispro, and glulisine all are specifically
approved for pump use.
https://www.youtube.com/watch?v=ASQo9bIPch4
69. Complications of Insulin Therapy
1. Hypoglycemia: Due to carbohydrate consumption, unusual
physical exertion, or too large dose of insulin.
2. Wt gain: Due to caloric storage of glucose by insulin, and some
is due to renal sodium retention resulting in fluid retention and
is due to renal sodium retention resulting in fluid retention and
edema
3. Insulin allergy: Due to histamine release from tissue mast cells
sensitized by anti-insulin IgE antibodies
4. Lipodystrophy: Due to injecting repeatedly at the same site.
73. INSULIN SECRETAGOGUES:
1. SULFONYLUREAS
Mechanism of Action :
A.
Sulfonylureas
↓
Inhibits the efflux of potassium ions
Inhibits the efflux of potassium ions
↓
Depolarization.
↓
Opens a voltage-gated calcium channel
↓
Calcium influx and the release of preformed insulin
B. Reduction of Serum Glucagon Concentrations
74. FIRST-GENERATION SULFONYLUREAS
Tolbutamide
•well absorbed but rapidly metabolized in the liver.
•Elimination half-life of 4–5 hours, and it is best administered in
divided doses. Because of its short half-life, it is the safest
divided doses. Because of its short half-life, it is the safest
sulfonylurea for elderly diabetics.
•Prolonged hypoglycemia has been reported rarely, mostly in
patients receiving certain drugs (eg, dicumarol, phenylbutazone,
some sulfonamides) that inhibit the metabolism of tolbutamide
75. Chlorpropamide
•Half-life of 32 hours and is slowly metabolized in the liver.
•Approximately 20–30% is excreted unchanged in the urine.
•Chlorpropamide also interacts with dicumarol, phenylbutazone,
some sulfonamides that depend on hepatic oxidative catabolism, and
•It is contraindicated in patients with hepatic or renal insufficiency.
Adverse effect:
1. Dosage higher than 500 mg daily increase the risk of jaundice.
2. Hyperemic flush after alcohol ingestion
3. dilutional hyponatremia
76. 2. MEGLITINIDE
•Because of its rapid onset, repaglinide is indicated for use in
controlling postprandial glucose excursions. taken just before each
meal
•There is no sulfur in its structure, so repaglinide may be used in
•There is no sulfur in its structure, so repaglinide may be used in
type 2 diabetics with sulfur or sulfonylurea allergy.
77. BIGUANIDES
Mechanisms of Action
•Reduction in hepatic glucose production through activation of the
•Reduction in hepatic glucose production through activation of the
enzyme AMP-activated protein kinase (AMPK).
• Impairment of renal gluconeogenesis.
• Slowing of glucose absorption from the gastrointestinal tract.
• Direct stimulation of glycolysis in tissues
• Increased glucose removal from blood, and reduction of plasma
glucagon levels.
78. Mechanism of Biguanide :
AMPK is a critical cellular energy sensor and regulator of
energy homeostasis
Metformin stimulates AMPK
↓
Inhibition of glucose production in rat primary hepatocytes.
↓
Reduce blood glucose level
79. Clinical Use
•Biguanides are recommended as first-line therapy for type 2 diabetes.
Because metformin does not increase body weight or provoke
hypoglycemia, it offers obvious advantages over insulin or
sulfonylureas.
•The UKPDS (United Kingdom Prospective Diabetes Study) reported
that metformin therapy decreases the risk of macrovascular as well as
that metformin therapy decreases the risk of macrovascular as well as
microvascular disease.
•Biguanides are also indicated for use in combination with insulin
secretagogues or thiazolidinediones in type 2 diabetics in whom oral
monotherapy is inadequate.
•Metformin is efficacious in preventing the new onset of type 2 diabetes
in middle-aged, obese persons with impaired glucose tolerance and
fasting hyperglycemia.
82. THIAZOLIDINEDIONES
a. Pioglitazone and
b. Rosiglitazone
Thiazolidinediones (Tzds) act to decrease insulin resistance through
peroxisome proliferator-activated receptor gamma (PPAR-γ). PPARγ
stimulation up regulates the expression of genes involved in lipid &
glucose metabolism, insulin signal transduction, and adipocyte
differentiation.
83. Adverse effect:
• Fluid retention: Due to reduction in renal excretion of sodium
and an increase in sodium and free water retention .
• Heart failure
• Loss of bone mineral density and increased atypical extremity
bone fractures.
bone fractures.
Atypical extremity femoral fractures
84. Exenatide is a synthetic version of exendin-4, a peptide found in the saliva of th
e Gila monster.
•M/A: Exenatide mimics the effects of GLP-1 , but is longer acting.
• It lowers blood glucose after a meal by increasing insulin secretion, suppressing
glucagon secretion and slowing gastric emptying .
•It reduces food intake (by an effect on satiety) and is associated with modest
weight loss.
• It reduces hepatic fat accumulation.
Glucagon-like peptide-1 (GLP-1) receptor agonists
• It reduces hepatic fat accumulation.
Pharmacokinetics: Exenatide is not absorbed by the gut and is administered s
ubcutaneously. It is much more stable than GLP-1, and is administered twice dail
y before the first and last meal of the day. A long-acting preparation (for once-we
ekly administration) is under investigation . It can cause hypoglycaemia and a ran
ge of gastrointestinal effects.
Pancreatitis is a rare but sometimes severe problem.
Indication:
Exenatide is used in patients with type 2 diabetes in combination with metformin
with or without a sulfonylurea when these have been inadequate.
85. Glucagon-like peptide-1 (GLP-1) receptor agonists :
Exenatide, Liraglutide
• Potentiating the incretin GLP- 1 mediated insulin secretion:
As GLP-1 binds to receptors on the pancreatic β cells
↓
activates adenylate cyclase that increases the production of cAMP from ATP
activates adenylate cyclase that increases the production of cAMP from ATP
Activation of secondary pathways
↓
alters the ion channel activity causes elevated levels of cytosolic Ca2+
• Suppression of postprandial glucagon release
• Slowed gastric emptying, and a
• Central loss of appetite.
86. DI-PEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS
sitagliptin, vildagliptin
M/A: Gliptins are synthetic drugs that competitively inhibit dipepti
dylpeptidase-4 (DPP-4), thereby lowering blood glucose by potentia
ting endogenous incretins .
PK:
PK:
• Sitagliptin does not cause weight loss or weight gain.
• Sitagliptin is well absorbed from the gut and is administered once
daily by mouth.
•It is mainly eliminated by renal excretion and is also metabolized
by hepatic CYP enzymes. It is well tolerated .
Indication:
Sitagliptin is used for type 2 diabetes, usually in addition to other
oral hypoglycaemic drugs.
87. ALPHA-GLUCOSIDASE INHIBITORS (Acarbose and miglitol )
Mechanism of action:
Competitive inhibitors of the intestinal α-glucosidases , enteric
enzymes that are attached to the brush border of the intestinal cells
↓
↓
Delaying the digestion and absorption of starch and disaccharides
↓
reduce postmeal glucose excursions
Adverse effects:
• Flatulence
• Diarrhea, and
•Abdominal pain
88. AMYLIN ANALOG : Pramlintide ,
• A synthetic analog of amylin, is an injectable antihyperglycemic
agent.
• Modulates postprandial glucose levels and is approved for
preprandial use in persons with type 1 and type 2 diabetes in
addition to insulin.
•An analog of amylin, pramlintide, differs from amylin by the
substitution of proline at positions 25, 28, and 29. These
modifications make pramlintide soluble and non–self-aggregating,
and suitable for pharmacologic use.
.
89. Mechanism of action:
Pramlintide
• Suppresses glucagon release.
• Delays gastric emptying.
• Central nervous system mediated anorectic
• Central nervous system mediated anorectic
effects.
Adverse effects:
• Hypoglycemia and
• Gastrointestinal symptoms, including
nausea, vomiting, and anorexia.