The document discusses the brain's role in glucose homeostasis. It begins with a historical perspective on the discovery of the brain's endocrine functions in glucose regulation in the 19th century. It then outlines the brain's control of glucose homeostasis through various hypothalamic centers that regulate peripheral organs like the liver. Specifically, it describes the brain-centered glucoregulatory system (BCGS) that maintains glucose levels through direct and indirect control of hepatic glucose production. The document also discusses the concept of glucose effectiveness and potential dysfunctions in the BCGS that can lead to diabetes.
Insulin is a hormone produced by beta cells in the pancreas that regulates glucose levels. It is composed of two chains of amino acids that are linked together. Glucose triggers the release of insulin which binds to receptors on cells to stimulate glucose and amino acid uptake and inhibit gluconeogenesis. Diabetes occurs when there is insufficient insulin production or the body does not respond properly to insulin, leading to high blood glucose levels and damage to organs over time. The two main types are type 1 diabetes caused by autoimmune destruction of beta cells, and type 2 diabetes related to insulin resistance.
Modelling the Variability in the Insuline-Glucose Feedback SystemVicente RIBAS-RIPOLL
This document discusses a mathematical model of the insulin-glucose feedback system. The model aims to describe the dynamic relationships between blood glucose concentration, insulin, and other hormones under various metabolic conditions. It represents insulin secretion from pancreatic beta cells as bursting oscillations driven by bistability in the cells. The model predicts ultradian oscillations in glucose and insulin levels consistent with real data. Analysis of the model's dynamics reveals two Hopf bifurcations that could explain physiological oscillations. Future work will refine the model and estimate parameter values to better predict glucose variability.
This document discusses diabetes mellitus and insulin. It defines the two major types of diabetes as Type 1 (caused by beta cell destruction) and Type 2 (caused by relative beta cell deficiency and decreased tissue sensitivity). The key signs and symptoms of diabetes are described. The discovery of insulin by Banting, Best, and others in the 1920s is summarized. The mechanisms of action, absorption, and types of insulin are outlined. Factors affecting glucose homeostasis and the treatment of diabetes with insulin are also summarized.
Insulin is a peptide hormone, produced by beta cells of the pancreas, and is central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, skeletal muscles, and fat tissue to absorb glucose from the blood. In the liver and skeletal muscles, glucose is stored as glycogen, and in fat cells (adipocytes) it is stored as triglycerides.
Frederick Banting had the idea that led to the discovery of insulin. He performed surgeries on dogs with Charles Best assisting. Before insulin, physicians endorsed fasting and low-calorie diets for diabetes, which provided some relief but death often followed. The first human given insulin was Leonard Thompson in 1922. Later, Frederick Sanger determined insulin's structure, winning a Nobel Prize in 1958. Rosalyn Yalow developed radioimmunoassay, allowing accurate insulin measurement, earning her a 1977 Nobel Prize. Today, recombinant DNA technology produces human insulin.
Insulin is a polypeptide hormone composed of two chains of amino acids that is produced by beta cells in the pancreas. It plays an important role in regulating blood glucose levels. Insulin binds to receptors on cells and signals the translocation of glucose transporters to cell membranes, allowing glucose uptake. It also stimulates the synthesis of enzymes involved in glycolysis. Diabetes occurs when the body does not produce enough insulin or the cells ignore the insulin signal, resulting in high blood glucose levels. The document provides details on the structure, function, biosynthesis and role of insulin.
This research article investigates how circulating glucose levels modulate neural control of the desire for high-calorie foods in humans. The study found that:
1) Mild hypoglycemia preferentially activated brain regions involved in reward and motivation (e.g. striatum, insula) and increased reported desire for high-calorie foods, compared to a state of euglycemia.
2) Euglycemia preferentially activated brain regions involved in inhibitory control (e.g. prefrontal cortex, anterior cingulate cortex) and resulted in less interest in food stimuli.
3) Higher circulating glucose levels predicted greater activation of the medial prefrontal cortex, and this response was absent in obese
Insulin is a hormone produced by beta cells in the pancreas that regulates glucose levels. It is composed of two chains of amino acids that are linked together. Glucose triggers the release of insulin which binds to receptors on cells to stimulate glucose and amino acid uptake and inhibit gluconeogenesis. Diabetes occurs when there is insufficient insulin production or the body does not respond properly to insulin, leading to high blood glucose levels and damage to organs over time. The two main types are type 1 diabetes caused by autoimmune destruction of beta cells, and type 2 diabetes related to insulin resistance.
Modelling the Variability in the Insuline-Glucose Feedback SystemVicente RIBAS-RIPOLL
This document discusses a mathematical model of the insulin-glucose feedback system. The model aims to describe the dynamic relationships between blood glucose concentration, insulin, and other hormones under various metabolic conditions. It represents insulin secretion from pancreatic beta cells as bursting oscillations driven by bistability in the cells. The model predicts ultradian oscillations in glucose and insulin levels consistent with real data. Analysis of the model's dynamics reveals two Hopf bifurcations that could explain physiological oscillations. Future work will refine the model and estimate parameter values to better predict glucose variability.
This document discusses diabetes mellitus and insulin. It defines the two major types of diabetes as Type 1 (caused by beta cell destruction) and Type 2 (caused by relative beta cell deficiency and decreased tissue sensitivity). The key signs and symptoms of diabetes are described. The discovery of insulin by Banting, Best, and others in the 1920s is summarized. The mechanisms of action, absorption, and types of insulin are outlined. Factors affecting glucose homeostasis and the treatment of diabetes with insulin are also summarized.
Insulin is a peptide hormone, produced by beta cells of the pancreas, and is central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, skeletal muscles, and fat tissue to absorb glucose from the blood. In the liver and skeletal muscles, glucose is stored as glycogen, and in fat cells (adipocytes) it is stored as triglycerides.
Frederick Banting had the idea that led to the discovery of insulin. He performed surgeries on dogs with Charles Best assisting. Before insulin, physicians endorsed fasting and low-calorie diets for diabetes, which provided some relief but death often followed. The first human given insulin was Leonard Thompson in 1922. Later, Frederick Sanger determined insulin's structure, winning a Nobel Prize in 1958. Rosalyn Yalow developed radioimmunoassay, allowing accurate insulin measurement, earning her a 1977 Nobel Prize. Today, recombinant DNA technology produces human insulin.
Insulin is a polypeptide hormone composed of two chains of amino acids that is produced by beta cells in the pancreas. It plays an important role in regulating blood glucose levels. Insulin binds to receptors on cells and signals the translocation of glucose transporters to cell membranes, allowing glucose uptake. It also stimulates the synthesis of enzymes involved in glycolysis. Diabetes occurs when the body does not produce enough insulin or the cells ignore the insulin signal, resulting in high blood glucose levels. The document provides details on the structure, function, biosynthesis and role of insulin.
This research article investigates how circulating glucose levels modulate neural control of the desire for high-calorie foods in humans. The study found that:
1) Mild hypoglycemia preferentially activated brain regions involved in reward and motivation (e.g. striatum, insula) and increased reported desire for high-calorie foods, compared to a state of euglycemia.
2) Euglycemia preferentially activated brain regions involved in inhibitory control (e.g. prefrontal cortex, anterior cingulate cortex) and resulted in less interest in food stimuli.
3) Higher circulating glucose levels predicted greater activation of the medial prefrontal cortex, and this response was absent in obese
Before the discovery of insulin in 1921, people with type 1 diabetes died within weeks to years of disease onset. In the early 1900s, attempts were made to treat diabetes with pancreatic extracts with temporary success. In 1921-1922, Banting, Best, Macleod, and Collip discovered insulin by extracting it from pancreatic islets, and tested it successfully on the first patient Leonard Thompson. Insulin production began commercially in 1922 and significantly increased life expectancy for people with diabetes from average ages of 11-34 years before insulin to 45-65 years by the 1940s.
The mechanisms involved in body weight regulation in humans include genetic, physiological, and behavioral factors. Stability of body weight and body composition requires that energy intake matches energy expenditure and that nutrient balance is achieved. Human obesity is usually associated with high rates of energy expenditure. In adult individuals, protein and carbohydrate stores vary relatively little, whereas adipose tissue mass may change markedly. A feedback regulatory loop with three distinct steps has been recently identified in rodents: 1) a sensor that monitors the size of adipose tissue mass is represented by the amount of leptin synthesized by adipose cells (a protein encoded by the ob gene) which determines the plasma leptin levels;2) hypothalamic centers, with specific leptin receptors, which receive and integrate the intensity of the signal; and3) effector systems that influence the two determinants of energy balance, i.e., energy intake and energy expenditure. With the exception of a few very rare cases, the majority of obese human subjects have high plasma leptin levels that are related to the size of their adipose tissue mass. However, the expected regulatory responses (reduction in food intake and increase in energy expenditure) are not observed in obese individuals. Thus obese humans are resistant to the effect of endogenous leptin, despite unaltered hypothalamic leptin receptors. Whether defects in the leptin signaling cascade play a role in the development of human obesity is a field of great actual interest that needs further research. Present evidences suggest that genetic and environmental factors influence eating behavior of people prone to obesity and that diets that are high in fat or energy dense undermine body weight regulation by promoting an overconsumption of energy relative to need.
#APS
The document discusses insulin, its biosynthesis and secretion, types of insulin preparations, and management of diabetes. It covers:
1) How insulin is synthesized and secreted in the pancreas and the three products - proinsulin, C-peptide, and insulin.
2) Factors that stimulate and inhibit insulin secretion.
3) Different types of insulin preparations including short-acting, intermediate-acting, long-acting, and premixed insulins.
4) Treatment of diabetes including insulin therapy, oral hypoglycemic agents, monitoring of blood glucose and HbA1c levels.
This presentation is just an overview/summary of the vast topic insulin , its biosynthesis , mechanism of action , effects of insulin on body , related diseases and marketed preparations of insulin.
Insulin is a hormone produced by the pancreas that regulates blood sugar levels. It allows the body to use and store carbohydrates from food. Without enough insulin, blood sugar levels rise and a person develops diabetes. There are different types of insulin that work in various timeframes to mimic the body's natural insulin release and keep blood sugar stable. Insulin is essential for diabetes treatment but requires careful dosing to avoid hypoglycemia from too much insulin or hyperglycemia from too little insulin. New delivery methods like insulin pens and pumps aim to more closely match a person's changing insulin needs.
This document summarizes key aspects of insulin including its history, structure, biosynthesis, transport, degradation, effects, and clinical correlations. It describes how insulin was first extracted from dog pancreases in 1921. Insulin is a polypeptide hormone composed of two chains that are held together. It regulates carbohydrate, lipid, and protein metabolism. Insulin increases glucose uptake and storage while decreasing gluconeogenesis. Clinically, insufficient insulin production can lead to symptoms of diabetes like frequent urination.
Insulin is a hormone produced by beta cells in the pancreas that regulates blood glucose levels. There are different types of insulin classified by source and duration of action that are used to treat diabetes, from fast-acting to long-lasting varieties. Insulin administration through injection or pump must be carefully titrated to each patient's needs and lifestyle to control blood sugar without causing hypoglycemia. Complications can arise from improper insulin dosing or resistance.
This document discusses newer insulin preparations that have been developed through genetic engineering to better mimic the body's natural insulin secretion patterns. It introduces several newer rapid-acting and long-acting insulin analogs such as insulin lispro, insulin aspart, insulin glargine, and insulin detemir. These analogs were designed to have faster onset of action, shorter duration, or longer duration compared to older insulin preparations. The document also briefly discusses inhaled insulin and newer advances in insulin delivery technologies.
Short term satiety is regulated by mechano- and chemoreceptors in the stomach and small intestine that signal fullness after eating. Hormones like CCK, GLP-1, PYY are also involved in short term regulation by being released from the gut in response to food intake. Long term satiety is regulated by hormones like leptin released by adipose tissue and signals fullness over longer periods based on fat stores. Both short term gut signals and long term adipose signals need to work together to properly regulate long term energy balance and food intake.
Insulin degludec is an ultralong-acting basal insulin analogue administered via once daily subcutaneous injection to help control blood sugar levels in diabetes. It has a duration of action of up to 40 hours, making it suitable as a once-daily treatment. Clinical trials found it to be as effective as insulin glargine at reducing HbA1c levels while having a lower risk of hypoglycemia, especially nocturnal hypoglycemia. Insulin peglispro is an experimental basal insulin consisting of insulin lispro covalently attached to polyethylene glycol. Phase II clinical trials found it reduced blood glucose variability compared to insulin glargine while maintaining similar HbA1c lowering and hypoglycemia rates,
This document discusses glucose homeostasis and diabetic emergencies from an emergency perspective. It provides guidance on assessing altered mental status, including checking a blood sugar level. It describes insulin and its role in glucose metabolism. Diabetic ketoacidosis and hyperglycemic hyperosmolar state are life-threatening disorders that can result from lack of insulin or inability to use insulin properly. Proper treatment involves fluid resuscitation and insulin therapy while closely monitoring electrolytes. Hypoglycemia is also covered, noting it can result if insulin levels are too high.
This document presents information about diabetes and the production of insulin. It discusses the history of extracting insulin from animals, the limitations of this process, and the development of recombinant DNA technology to produce human insulin in bacteria. This allowed large-scale production of insulin without relying on animal sources. The document also describes efforts to develop improved second generation recombinant insulins through protein engineering to provide faster acting versions for treatment of diabetes.
Treatment of Type 1 Diabetes mellitus involves lifelong insulin administration. Insulin is produced in the pancreas and regulates blood glucose levels. Type 1 diabetes results from autoimmune destruction of insulin-producing pancreatic beta cells leading to complete insulin deficiency. Various insulin preparations have been developed with differing durations of action to mimic normal insulin secretion. Treatment involves calculating total daily insulin dose and dividing into short and long-acting insulins administered multiple times daily. Adverse effects and methods to overcome insulin resistance are also discussed.
This document provides information on insulin therapy. It discusses what insulin is, how it is secreted normally, and its actions in the body. Insulin deficiency results in hyperglycemia and other metabolic defects. The discovery of insulin by Banting and Best in 1921 revolutionized the treatment of diabetes. Insulin comes in various forms including rapid-acting, short-acting, intermediate-acting, long-acting, and premixed varieties. Common insulin regimens include split-mixed, basal, basal-plus, and basal-bolus. Early initiation of insulin in type 2 diabetes has clinical benefits beyond glycemic control. Barriers to insulin therapy include fear of hypoglycemia and the inconvenience of injection schedules. Pro
New therapies in diabetes mellitus include GLP-1 receptor agonists (incretin based therapy), SGLT2 inhibitors, newer basal insulins like insulin degludec, and artificial pancreas systems. GLP-1 agonists have benefits like potential preservation of beta cell function, weight loss, decreased blood pressure and improved lipid profile but side effects include GI intolerance and risk of pancreatitis. SGLT2 inhibitors improve glucose control by increasing urinary glucose excretion and have benefits of weight loss and blood pressure reduction. Insulin degludec has a long duration of action of over 42 hours allowing once daily dosing. Artificial pancreas systems aim to mimic physiological insulin delivery but current devices
The document discusses the physiological basis for control of appetite and body weight. It describes how hunger, appetite, and satiety are regulated by the hypothalamus in response to signals from the gastrointestinal tract, adipose tissue, and hormones like ghrelin, leptin, insulin, and PYY. These signals influence centers in the hypothalamus that control food intake and energy balance on both a short term and long term basis. Dysregulation of these systems can lead to clinical conditions like obesity, eating disorders, and hyperphagia.
This document discusses insulin therapy, including its pharmacodynamics, mechanisms of action, types of insulin, insulin regimens, administration techniques, side effects, and patient education. Insulin is secreted by the pancreas and lowers blood glucose levels by facilitating glucose uptake into cells. It acts on the liver, muscle, adipose tissue, and other organs. Types include rapid, short, intermediate and long-acting insulins. Patient education focuses on proper administration, storage, monitoring, hypoglycemia treatment, and lifestyle factors.
By:Nader Al-assadi
Taiz university
Definition of weight loss:
Clinically important weight loss is defined as the loss of 10 pounds (4.5 kg) or >5% of one’s body weight over a period of 6–12 months.
Weight loss can be divided into 2 categories: involuntary or voluntary.
-1 Involuntary weight loss is a manifestation of cachexia associated with many disease states.
2- Voluntary weight loss, in the form of healthy dieting, is common among men and women. However, signifcant voluntary weight loss can herald a psychiatric illness such as an eating disorder, particularly among women.
K E Y T E R M S:
Anorexia Loss of the desire to eat.
Anorexia nervosa4 Intense fear of gaining weight and refusal to maintain weight at or above a minimally appropriate weight for height and age.
Bulimia nervosa4 Recurrent episodes of binge eating followed by recurrent compensatory behavior to prevent weight gain (ie, laxative abuse and self-induced vomiting).
Cachexia General muscle and/or fat wasting with malnutrition usually associated with chronic disease.
Involuntary weight loss The unintended loss of weight; sometimes not reported by the patient and only noted upon chart review.
Malnutrition Poor nutrition due to inadequate or unbalanced intake of nutrients or their impaired utilization.
Voluntary weight loss The conscious effort to lose weight; frequently not a complaint among those with eating disorders.
Homeostasis refers to the maintenance of stable internal conditions in the body. Glucose homeostasis specifically reflects a balance between hepatic glucose production and peripheral glucose uptake, regulated by insulin and glucagon. In the fasting state, low insulin and high glucagon promote gluconeogenesis and glycogenolysis in the liver to produce glucose for tissues like the brain that require it. Postprandially, high insulin and low glucagon stimulate glucose uptake in tissues and inhibit hepatic glucose production. Gluconeogenesis allows the conversion of substrates like lactate, glycerol, and amino acids into glucose, especially in the liver. It bypasses three irreversible glycolytic steps through key enzymes. The Cori and Alanine cycles shuttle lact
Before the discovery of insulin in 1921, people with type 1 diabetes died within weeks to years of disease onset. In the early 1900s, attempts were made to treat diabetes with pancreatic extracts with temporary success. In 1921-1922, Banting, Best, Macleod, and Collip discovered insulin by extracting it from pancreatic islets, and tested it successfully on the first patient Leonard Thompson. Insulin production began commercially in 1922 and significantly increased life expectancy for people with diabetes from average ages of 11-34 years before insulin to 45-65 years by the 1940s.
The mechanisms involved in body weight regulation in humans include genetic, physiological, and behavioral factors. Stability of body weight and body composition requires that energy intake matches energy expenditure and that nutrient balance is achieved. Human obesity is usually associated with high rates of energy expenditure. In adult individuals, protein and carbohydrate stores vary relatively little, whereas adipose tissue mass may change markedly. A feedback regulatory loop with three distinct steps has been recently identified in rodents: 1) a sensor that monitors the size of adipose tissue mass is represented by the amount of leptin synthesized by adipose cells (a protein encoded by the ob gene) which determines the plasma leptin levels;2) hypothalamic centers, with specific leptin receptors, which receive and integrate the intensity of the signal; and3) effector systems that influence the two determinants of energy balance, i.e., energy intake and energy expenditure. With the exception of a few very rare cases, the majority of obese human subjects have high plasma leptin levels that are related to the size of their adipose tissue mass. However, the expected regulatory responses (reduction in food intake and increase in energy expenditure) are not observed in obese individuals. Thus obese humans are resistant to the effect of endogenous leptin, despite unaltered hypothalamic leptin receptors. Whether defects in the leptin signaling cascade play a role in the development of human obesity is a field of great actual interest that needs further research. Present evidences suggest that genetic and environmental factors influence eating behavior of people prone to obesity and that diets that are high in fat or energy dense undermine body weight regulation by promoting an overconsumption of energy relative to need.
#APS
The document discusses insulin, its biosynthesis and secretion, types of insulin preparations, and management of diabetes. It covers:
1) How insulin is synthesized and secreted in the pancreas and the three products - proinsulin, C-peptide, and insulin.
2) Factors that stimulate and inhibit insulin secretion.
3) Different types of insulin preparations including short-acting, intermediate-acting, long-acting, and premixed insulins.
4) Treatment of diabetes including insulin therapy, oral hypoglycemic agents, monitoring of blood glucose and HbA1c levels.
This presentation is just an overview/summary of the vast topic insulin , its biosynthesis , mechanism of action , effects of insulin on body , related diseases and marketed preparations of insulin.
Insulin is a hormone produced by the pancreas that regulates blood sugar levels. It allows the body to use and store carbohydrates from food. Without enough insulin, blood sugar levels rise and a person develops diabetes. There are different types of insulin that work in various timeframes to mimic the body's natural insulin release and keep blood sugar stable. Insulin is essential for diabetes treatment but requires careful dosing to avoid hypoglycemia from too much insulin or hyperglycemia from too little insulin. New delivery methods like insulin pens and pumps aim to more closely match a person's changing insulin needs.
This document summarizes key aspects of insulin including its history, structure, biosynthesis, transport, degradation, effects, and clinical correlations. It describes how insulin was first extracted from dog pancreases in 1921. Insulin is a polypeptide hormone composed of two chains that are held together. It regulates carbohydrate, lipid, and protein metabolism. Insulin increases glucose uptake and storage while decreasing gluconeogenesis. Clinically, insufficient insulin production can lead to symptoms of diabetes like frequent urination.
Insulin is a hormone produced by beta cells in the pancreas that regulates blood glucose levels. There are different types of insulin classified by source and duration of action that are used to treat diabetes, from fast-acting to long-lasting varieties. Insulin administration through injection or pump must be carefully titrated to each patient's needs and lifestyle to control blood sugar without causing hypoglycemia. Complications can arise from improper insulin dosing or resistance.
This document discusses newer insulin preparations that have been developed through genetic engineering to better mimic the body's natural insulin secretion patterns. It introduces several newer rapid-acting and long-acting insulin analogs such as insulin lispro, insulin aspart, insulin glargine, and insulin detemir. These analogs were designed to have faster onset of action, shorter duration, or longer duration compared to older insulin preparations. The document also briefly discusses inhaled insulin and newer advances in insulin delivery technologies.
Short term satiety is regulated by mechano- and chemoreceptors in the stomach and small intestine that signal fullness after eating. Hormones like CCK, GLP-1, PYY are also involved in short term regulation by being released from the gut in response to food intake. Long term satiety is regulated by hormones like leptin released by adipose tissue and signals fullness over longer periods based on fat stores. Both short term gut signals and long term adipose signals need to work together to properly regulate long term energy balance and food intake.
Insulin degludec is an ultralong-acting basal insulin analogue administered via once daily subcutaneous injection to help control blood sugar levels in diabetes. It has a duration of action of up to 40 hours, making it suitable as a once-daily treatment. Clinical trials found it to be as effective as insulin glargine at reducing HbA1c levels while having a lower risk of hypoglycemia, especially nocturnal hypoglycemia. Insulin peglispro is an experimental basal insulin consisting of insulin lispro covalently attached to polyethylene glycol. Phase II clinical trials found it reduced blood glucose variability compared to insulin glargine while maintaining similar HbA1c lowering and hypoglycemia rates,
This document discusses glucose homeostasis and diabetic emergencies from an emergency perspective. It provides guidance on assessing altered mental status, including checking a blood sugar level. It describes insulin and its role in glucose metabolism. Diabetic ketoacidosis and hyperglycemic hyperosmolar state are life-threatening disorders that can result from lack of insulin or inability to use insulin properly. Proper treatment involves fluid resuscitation and insulin therapy while closely monitoring electrolytes. Hypoglycemia is also covered, noting it can result if insulin levels are too high.
This document presents information about diabetes and the production of insulin. It discusses the history of extracting insulin from animals, the limitations of this process, and the development of recombinant DNA technology to produce human insulin in bacteria. This allowed large-scale production of insulin without relying on animal sources. The document also describes efforts to develop improved second generation recombinant insulins through protein engineering to provide faster acting versions for treatment of diabetes.
Treatment of Type 1 Diabetes mellitus involves lifelong insulin administration. Insulin is produced in the pancreas and regulates blood glucose levels. Type 1 diabetes results from autoimmune destruction of insulin-producing pancreatic beta cells leading to complete insulin deficiency. Various insulin preparations have been developed with differing durations of action to mimic normal insulin secretion. Treatment involves calculating total daily insulin dose and dividing into short and long-acting insulins administered multiple times daily. Adverse effects and methods to overcome insulin resistance are also discussed.
This document provides information on insulin therapy. It discusses what insulin is, how it is secreted normally, and its actions in the body. Insulin deficiency results in hyperglycemia and other metabolic defects. The discovery of insulin by Banting and Best in 1921 revolutionized the treatment of diabetes. Insulin comes in various forms including rapid-acting, short-acting, intermediate-acting, long-acting, and premixed varieties. Common insulin regimens include split-mixed, basal, basal-plus, and basal-bolus. Early initiation of insulin in type 2 diabetes has clinical benefits beyond glycemic control. Barriers to insulin therapy include fear of hypoglycemia and the inconvenience of injection schedules. Pro
New therapies in diabetes mellitus include GLP-1 receptor agonists (incretin based therapy), SGLT2 inhibitors, newer basal insulins like insulin degludec, and artificial pancreas systems. GLP-1 agonists have benefits like potential preservation of beta cell function, weight loss, decreased blood pressure and improved lipid profile but side effects include GI intolerance and risk of pancreatitis. SGLT2 inhibitors improve glucose control by increasing urinary glucose excretion and have benefits of weight loss and blood pressure reduction. Insulin degludec has a long duration of action of over 42 hours allowing once daily dosing. Artificial pancreas systems aim to mimic physiological insulin delivery but current devices
The document discusses the physiological basis for control of appetite and body weight. It describes how hunger, appetite, and satiety are regulated by the hypothalamus in response to signals from the gastrointestinal tract, adipose tissue, and hormones like ghrelin, leptin, insulin, and PYY. These signals influence centers in the hypothalamus that control food intake and energy balance on both a short term and long term basis. Dysregulation of these systems can lead to clinical conditions like obesity, eating disorders, and hyperphagia.
This document discusses insulin therapy, including its pharmacodynamics, mechanisms of action, types of insulin, insulin regimens, administration techniques, side effects, and patient education. Insulin is secreted by the pancreas and lowers blood glucose levels by facilitating glucose uptake into cells. It acts on the liver, muscle, adipose tissue, and other organs. Types include rapid, short, intermediate and long-acting insulins. Patient education focuses on proper administration, storage, monitoring, hypoglycemia treatment, and lifestyle factors.
By:Nader Al-assadi
Taiz university
Definition of weight loss:
Clinically important weight loss is defined as the loss of 10 pounds (4.5 kg) or >5% of one’s body weight over a period of 6–12 months.
Weight loss can be divided into 2 categories: involuntary or voluntary.
-1 Involuntary weight loss is a manifestation of cachexia associated with many disease states.
2- Voluntary weight loss, in the form of healthy dieting, is common among men and women. However, signifcant voluntary weight loss can herald a psychiatric illness such as an eating disorder, particularly among women.
K E Y T E R M S:
Anorexia Loss of the desire to eat.
Anorexia nervosa4 Intense fear of gaining weight and refusal to maintain weight at or above a minimally appropriate weight for height and age.
Bulimia nervosa4 Recurrent episodes of binge eating followed by recurrent compensatory behavior to prevent weight gain (ie, laxative abuse and self-induced vomiting).
Cachexia General muscle and/or fat wasting with malnutrition usually associated with chronic disease.
Involuntary weight loss The unintended loss of weight; sometimes not reported by the patient and only noted upon chart review.
Malnutrition Poor nutrition due to inadequate or unbalanced intake of nutrients or their impaired utilization.
Voluntary weight loss The conscious effort to lose weight; frequently not a complaint among those with eating disorders.
Homeostasis refers to the maintenance of stable internal conditions in the body. Glucose homeostasis specifically reflects a balance between hepatic glucose production and peripheral glucose uptake, regulated by insulin and glucagon. In the fasting state, low insulin and high glucagon promote gluconeogenesis and glycogenolysis in the liver to produce glucose for tissues like the brain that require it. Postprandially, high insulin and low glucagon stimulate glucose uptake in tissues and inhibit hepatic glucose production. Gluconeogenesis allows the conversion of substrates like lactate, glycerol, and amino acids into glucose, especially in the liver. It bypasses three irreversible glycolytic steps through key enzymes. The Cori and Alanine cycles shuttle lact
This document summarizes several anti-obesity drugs that are approved or being studied for the treatment of obesity. It discusses the efficacy, safety and clinical insights for drugs like Orlistat, Liraglutide, Naltrexone/Bupropion, Diethylpropion, Setmelanotide. It also discusses the central and peripheral mechanisms of action of various anti-obesity drugs and potential treatment approaches for rare genetic conditions like Bardet-Biedl syndrome.
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.
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.
The document discusses hormonal regulation of blood glucose levels. It explains that insulin, glucagon, and epinephrine work to keep blood glucose within a narrow range. Insulin is released when glucose is high and signals cells to take up and store glucose. Glucagon is released when glucose is low and signals the liver to produce glucose through gluconeogenesis and glycogen breakdown. Epinephrine prepares the body for activity by stimulating glycogen and fat breakdown. Diabetes results from defects in insulin production or action, leading to high blood glucose and ketone production. Prolonged fasting relies on gluconeogenesis and ketone bodies for fuel. Alcohol excess can cause hypoglycemia by inhibiting gluconeogenesis in the liver.
Regulation of metabolic pathways at whole cell level. It encloses basic understanding of use and the need for regulation. Emphasis is given on glycogen metabolism and the changes a cell undergoes in fed and fasting state. Regulation of various metabolic pathways make sure the cell survives in a particular condition.
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.
The pancreas contains both exocrine cells that secrete enzymes for digestion and endocrine cells clustered in islets of Langerhans that secrete hormones. The beta cells within the islets secrete insulin, which regulates blood glucose levels. Insulin binds to receptors on cells to promote glucose uptake and storage and regulate metabolism. Glucagon from alpha cells has opposing actions, raising blood glucose. Precise balance of insulin and glucagon maintains normal glucose homeostasis, while diabetes results from insufficient insulin.
This document discusses glucose homeostasis and the maintenance of blood glucose levels. It explains that glucose homeostasis relies on a balance between glucose production in the liver and uptake by tissues. Insulin is a key regulator that promotes glucose uptake after meals and inhibits production during fasting. Other hormones like glucagon stimulate production when glucose levels drop. The document outlines the complex mechanisms that keep blood glucose within a narrow range to ensure the brain has a continuous supply while allowing for variations from meals and activity.
Blood sugar homeostasis is maintained through a balance of hepatic glucose production and peripheral glucose uptake regulated by hormones like insulin and glucagon. In the fasting state, low insulin and high glucagon promote gluconeogenesis and glycogenolysis to increase glucose production. After eating, high insulin and low glucagon stimulate glucose uptake in tissues and inhibit production. Disruptions can cause hyperglycemia or hypoglycemia.
This document discusses the pathogenesis and etiology of metabolic disorders, including disorders of carbohydrate and lipid metabolism. It covers several key points:
1. Metabolic disorders can be caused by genetic factors like enzymopathies, damage to membranes/receptors, endocrine dysfunction, and neural impairment.
2. Dietary and digestive issues as well as other organ dysfunction can also contribute to metabolic disorders.
3. Glucose regulation is maintained through a balance of insulin and counter-regulatory hormones like glucagon, with disorders resulting in hyperglycemia or hypoglycemia.
4. The two primary types of diabetes mellitus - type 1 and type 2 - differ in etiology and pathogenesis
This document provides an overview of blood glucose regulation and diabetes. It begins with definitions of key terms like blood sugar, normal glucose levels, and hyperglycemia and hypoglycemia. The document then discusses the history of diabetes research and discoveries. It explains the normal physiology of glucose regulation including the roles of insulin, glucagon, and other hormones. It also covers alterations in blood glucose levels and the public health impacts of diabetes.
Describe neuroendocrine regulation of energy metabolism during the fed state
Discuss regulation of energy metabolism during the fasted state.
List the counter-regulatory hormones and describe their effects.
Discuss the Maintenance of Long-Term Energy Balance & Fat Storage
Correlate this knowledge to the related clinical conditions.
1. Type 2 diabetes results from insulin resistance in the liver and peripheral tissues like muscle, as well as relative insulin deficiency. This leads to elevated hepatic glucose production and reduced glucose uptake in tissues.
2. Sustained hyperglycemia can cause glucotoxicity and further impair insulin secretion and action, exacerbating the disease. It also increases renal glucose reabsorption above normal levels, causing glucosuria.
3. Over time, this pathophysiology can damage target organs and increase the risk of diabetes complications if not properly treated. Treatment aims to reduce hyperglycemia through medications that increase insulin secretion and action or decrease hepatic glucose production.
1. Type 2 diabetes results from insulin resistance in the liver and peripheral tissues like muscle, as well as relative insulin deficiency. This leads to increased hepatic glucose production and reduced glucose uptake in tissues.
2. Sustained hyperglycemia can cause glucotoxicity and further impair insulin secretion and action, exacerbating the disease. It also increases renal glucose reabsorption beyond the renal threshold, causing glucosuria.
3. Over time, this pathophysiology can cause impaired counterregulatory hormone responses to hypoglycemia, increasing the risk of severe and prolonged hypoglycemic episodes with loss of symptomatic awareness.
This document discusses glucose homeostasis and the tightly regulated process of maintaining blood glucose levels within a narrow range. It describes the various sources of blood glucose, including dietary carbohydrates and the body's ability to produce glucose through glycogenolysis and gluconeogenesis when needed. Key hormones involved in regulating glucose include insulin, released after meals to lower blood glucose levels, and glucagon, released during fasting to raise blood glucose levels and promote glycogen breakdown and glucose production. Precise control of these opposing hormones is critical for metabolic health.
This document discusses the entero-insular axis, which refers to the gut factors that contribute to enhanced insulin secretion after eating a meal. It has neural, endocrine, and metabolic components. Neural factors like cholinergic innervation account for 20% of the insulin response, while hormonal factors like GLP-1 and GIP account for 30%. These hormones are secreted from the gut in response to food ingestion and stimulate insulin secretion from pancreatic beta cells in a glucose-dependent manner. They also inhibit glucagon secretion and slow gastric emptying. The document further discusses the roles of various nutrients like carbohydrates, proteins, and fatty acids in stimulating insulin secretion and their implications for diabetes treatment and management.
The document summarizes the regulation of blood glucose levels. It discusses how glucose levels are maintained within a narrow range through negative feedback involving the pancreas and hormones like insulin and glucagon. Insulin regulates glucose by promoting its uptake in tissues and storage, while glucagon stimulates glucose production when levels fall. Glucose comes from digestion, liver glycogen stores, and gluconeogenesis. Factors that increase or decrease blood glucose levels are also outlined.
Mr. AH is a 70-year-old man who was diagnosed with T2DM 10 years ago. He was initially treated with lifestyle management and metformin.
3 years later, his doctors advised him to add long acting basal insulin analogue to metformin, reached to 40U/day .
Other current medical conditions include: hypertension, hypothyroidism, and mild osteoporosis without fracture history.
Current medications; Metformin 1000 mg bid, long acting basal insulin analogue 40U/day , Candesartan 16 mg qd, Alendronate 70 mg once weekly, Levothyroxine 100 mg qd.
Physical exam: BMI 26 kg/m2, BP 140/80 mmHg, otherwise unremarkable.
His current FPG 140 mg/dL and HbA1c 8.5%. Kidney and liver functions are normal.
Disturbances of piturtary adrenal gonadal axis in hemodialysis ptalaa wafa
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In CRF, there are complex endocrinal disorders related to hypothalamus and pituitary functions, and their relations to adrenal and gonadal functions also as far as sex hormones and adipose tissue hormones .
There is a great need for more randomized clinical trials to evaluate new and old treatment approaches, with the goal of developing better evidence-based practice guidelines.
Diabetic nephropathy considered one of the most common complications of DM. This presentation answer the question are some diabetic patient immune to diabetic nephroapthy
This document discusses the management of diabetes in patients with concomitant liver disease. It notes that about half of patients with cirrhosis have diabetes due to insulin resistance caused by the liver disease. Lifestyle changes and metformin are recommended initially if liver disease is mild. Insulin, sulfonylureas, meglitinides, alpha-glucosidase inhibitors, and thiazolidinediones may be used, with monitoring needed due to potential side effects or altered drug metabolism in liver disease. Insulin requirements can vary depending on the stage of liver disease.
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Hypothyroidism symptoms include fatigue and weight gain. Hashimoto's thyroiditis is a common cause of autoimmune hypothyroidism. Laboratory tests show increased T
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Fasting Ramadan carry many hazards to diabetic need to fast. Uncontrolled patients have a liability to some dangerous complications like DKA,HYPOGLYCEMIA,HHS AND thromboembolism
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This document discusses guidelines for the treatment of dyslipidemia. It begins by comparing hypertension treatment to lipid lowering, noting that lipid lowering has fewer drug classes, mechanisms of action, and side effects compared to hypertension treatment. It then discusses how many patients do not reach lipid goals even after dose adjustments of statin medications. The document emphasizes the need for more effective cholesterol lowering to meet lipid goals. It reviews various studies demonstrating the relationship between cholesterol levels, cardiovascular risk, and mortality. It discusses the benefits of different statin medications and doses at lowering cholesterol. The document provides an overview of guideline recommendations for cholesterol goals and treatment intensities based on patient risk levels.
The document discusses the brain's role in glucose homeostasis. It begins with a historical perspective on the discovery of the brain's endocrine functions in glucose regulation in the 19th century. It then outlines the brain centers involved in glucose regulation, including glucose excited and inhibited neurons. The brain centered glucoregulatory system controls glucose homeostasis through direct and indirect regulation of hepatic glucose production. Dysfunctions in this system can lead to impaired glucose handling and diabetes. The document concludes by framing diabetes as a failure of both the brain centered and pancreatic centered glucoregulatory systems.
Peripheral Arterial Disease (PAD) is the progressive obstruction of arteries below the aortic bifurcation due to atherosclerosis. It has a prevalence of 5-20% in those over 50 years old. Symptoms range from intermittent claudication to critical limb ischemia with rest pain and tissue loss. Late presentation is common due to asymptomatic or atypical symptoms. Diabetes significantly increases the risk and severity of PAD. Treatment involves risk factor modification, endovascular or surgical revascularization, wound care, and in severe cases amputation. Regular screening and multidisciplinary care can help prevent amputation in those with PAD and foot ulcers.
C-peptide is a peptide that is cleaved from proinsulin during insulin synthesis and released from the pancreas in equal amounts to insulin. While previously thought to be biologically inert, C-peptide has been found to have effects on microvascular blood flow, tissue health, and cell signaling. It may play a therapeutic role in treating diabetes complications like neuropathy and nephropathy. Clinical uses of C-peptide testing include distinguishing type 1 from type 2 diabetes and monitoring endogenous insulin secretion. Ongoing clinical trials are exploring the potential benefits of C-peptide replacement therapy for type 1 diabetes complications.
Breastfeeding is recommended for infants for the first year and provides health benefits for both mother and baby. While sulfonylureas like glipizide cross the placenta during pregnancy, studies have found negligible or undetectable levels of glipizide and glyburide in breastmilk. Metformin is also considered safe during breastfeeding as studies have found low levels in breastmilk below 1% of the maternal dose, with no adverse effects seen in infants. Therefore, glipizide and metformin can be used during breastfeeding while managing diabetes.
Breastfeeding is recommended for infants for the first year of life and provides health benefits for both mother and baby. While sulfonylureas like glipizide were previously discouraged during breastfeeding due to transfer into breastmilk, recent studies found negligible levels of glyburide and glipizide in breastmilk. Metformin is also considered safe during breastfeeding as studies found low levels in breastmilk below 10% of the maternal dose, with no adverse effects seen in infants. Therefore, sulfonylureas and metformin appear to be compatible with breastfeeding for diabetic mothers.
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This SlideShare presentation provides a comprehensive overview of the Declaration of Helsinki, a foundational document outlining ethical guidelines for conducting medical research involving human subjects.
Mercurius is named after the roman god mercurius, the god of trade and science. The planet mercurius is named after the same god. Mercurius is sometimes called hydrargyrum, means ‘watery silver’. Its shine and colour are very similar to silver, but mercury is a fluid at room temperatures. The name quick silver is a translation of hydrargyrum, where the word quick describes its tendency to scatter away in all directions.
The droplets have a tendency to conglomerate to one big mass, but on being shaken they fall apart into countless little droplets again. It is used to ignite explosives, like mercury fulminate, the explosive character is one of its general themes.
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Brain as an endocrine organ
1. The Brain
as an Endocrine Organ
Alaa Wafa . MD
Associate Professor of Internal Medicine
Diabetes & Endocrine Unit.
Mansoura University
2. Agenda
• Historical perspective
• Brain control of glucose homeostasis
• Brain centerd glucoregulatory system (BCGS).
• Glucose effectiveness.
• Dysfunction in the BCGS.
• Conclusion
3. Agenda
• Historical perspective
• Brain control of glucose homeostasis
• Brain centered glucovregulatory system BCGS.
• Glucose effectiveness.
• Dysfunction in the BCGS.
• Conclusion
.
4. Claude Bernard
(1813-1878)
• Discovery of new
function of liver--
glucose secretion
into blood (1848)
• Previously thought
that only plants could
produce sugar
• Sugar must be taken
in by diet
5. Historical perspective
The first information regarding the role of
the central nervous system (CNS) in glucose
homeostasis dates from the 19th century, when
Claude Bernand 1854 showed that when
puncturing the flour of the fourth cerebral ventricle
in dogs he induced hyperglycemia.
6. Historical perspective
In 1953 Jean Mayer mentioned the existence of two
types of cells:
glucose excited (GE) neurons-activated by an
increase in glucose concentration
glucose inhibited (GI) neurons activated by a decrease
in glucose concentration.
7. Historical perspective
Twelve years later in 1965, ( during experiments on rabbits ),
Shimazu and his colleagues proved that electrical
stimulation of:
VMH (containing mainly sympathetic nuclei) up
regulated plasma glucose level and decreased hepatic
glycogen
LH (containing mainly parasympathetic nuclei) down
regulated plasma glucose and barely increased hepatic
glycogen.
8. Historical perspective
Further studies underlined the importance of CNS in
glucose metabolism:
• An increase in glucose level and hyperglycemic
hormones was seen after intracerebroventricular
administration of 2-deoxyglucose (2-DG), a glucose
antagonist. These effects were altered by
hypothalamic deafferentation.
• At the same time counterregulatory response
following insulin administration in dogs was blocked
once sectioning the spinal cord or the vagus
9. It is the maintenance of
blood glucose level
within the normal range
What is glucose
homeostasis???
10. Glucose Homeostasis
• brain has high consumption of glucose
• during exercise, working muscle competes
with brain for glucose
• Many redundant systems for maintaining
glucose homeostasis
• hepatic glucose production (glycogen, lactate,
pyruvate, glycerol, alanine)
• pancreatic hormones (insulin, glucagon)
• sympathoadrenal stimulation (epinephrine)
11. Agenda
• Historical perspective
• Brain control of glucose homeostasis
• Brain centerd glucoregulatory system BCGS.
• Glucose effectiveness.
• Dysfunction in the BCGS.
• Conclusion
.
14. CNS control of glucose homeostasis
• A large literature documents glucoregulatory
effects of pharmacological or genetic
interventions targeting neurons in any of
several areas of the hypothalamus (arcuate,
ventromedial and paraventricular
hypothalamic nuclei) and brain stem.
15.
16.
17. CNS control of glucose homeostasis
• Injection of insulin or glucose into discrete
hypothalamic areas can lower blood glucose
levels and increase liver insulin sensitivity.
• A similar effects are achieved by restoring
functional leptin receptors to specific
hypothalamic nuclei of animals that otherwise
lack them.
18. CNS control of glucose homeostasis
• Conversely, deletion of receptors for either
insulin or leptin (or their downstream
signalling intermediates) from defined
hypothalamic neurons causes glucose
intolerance and systemic insulin resistance.
These highlight how the brain can influence
glucose homeostasis in response to afferent
input from peripheral signals
?
19.
20. Control of hepatic glucose production
• Insulin regulates hepatic glucose
production (HGP) through a direct action
on hepatocytes, insulin has also been
proposed to regulate HGP via an indirect
mechanism involving insulin action at a
remote site.
23. Direct control of hepatic glucose
production
• The direct action of insulin on hepatocytes
involves its binding to insulin receptors and
activation of signal transduction cascades ,of
particular relevance to glycaemic control is
the insulin receptor substrate
phosphatidylinositol-3-OH kinase (IRS–PI(3)K)
pathway , which mediates insulin inhibition of
both glycogenolysis and gluconeogenesis, the
two primary determinants of HGP.
26. Indirect control of hepatic glucose
production
• The concept that HGP can also be controlled by insulin action at a
remote site was first proposed and received compelling support in
a recent study of ‘TLKO’ mice with hepatocytes unresponsive to
insulin owing to liver-specific deletion of key signal transduction
molecules (the two Akt isoforms as well as FOXO1).
• In these animals, insulin cannot directly regulate HGP via the Akt–
FOXO1 pathway. However, rather than exhibiting the expected loss
of regulation, both HGP and systemic glucose homeostasis are
controlled normally in these mice, even in response to exogenous
insulin.
27.
28. These data point to the existence of an indirect pathway through
which insulin and nutrients can regulate HGP even when
hepatocytes themselves are insensitive to direct insulin action.
An intriguing question is what mechanism mediates the indirect
control of HGP by insulin ?
Although other explanations are possible, the BCGS is both
activated by insulin and capable of regulating HGP in humans as
well as rodent modeL.
33. Agenda
• Historical perspective
• Brain control of glucose homeostasis
• Brain centerd glucoregulatory system BCGS.
• Glucose effectiveness.
• Dysfunction in the BCGS.
• Conclusion
.
34. The term glucose effectiveness (GE) refers to the effect of an
increased concentration of glucose to promote its own disposal,
independent of insulin action‘insulin-independent glucose disposal’.
It is noteworthy that, by definition, GE increases in response to rising
blood glucose levels, and that glucose action on arcuate nucleus
neurons has a rapid glucose-lowering effect.
35. Glucose Effectiveness
• Collectively, these observations support a model in
which, by increasing plasma concentrations of insulin,
leptin, GLP-1, FGF19 and glucose, consuming a meal
generates diverse signals that activate the BCGS.
• This BCGS activation then contributes to glucose
disposal via stimulation of both insulin-dependent and
-independent mechanisms that, together with islet
responses, are essential for proper glucose handling
by the body
38. Model of the hypothalamic regulation of hepatic glucose production.
Gregory J. Morton, and Michael W. Schwartz Physiol Rev 2011;91:389-411
39. CNS neurocircuits regulating energy and
glucose homeostasis.
Gregory J. Morton, and Michael W. Schwartz Physiol Rev 2011;91:389-411
40. GLP-1 activates brain areas in humans
that regulate food intake
Pannacciulli et al. Neuroimage 2007;35:511–7
PET scan of the hypothalamus
GLP-1, glucagon-like peptide-1; PET, positron emission tomography
41. For internal use Liraglutide is not approved for weight management
GLP-1 induces neuron activation in
multiple sites in the rat brain
Vehicle
Liraglutide
AP
NTS
Brain stem (receiving input from the intestine)
• Increased cFos in area postrema (AP) and nucleus
tractus solitarus (NTS)
Amygdala (associated with eating patterns)
• Increased cFos in the central amygdala
Hypothalamus (main appetite center in the brain)
• Increased cFos in the paraventricular nucleus
• Decreased cFos in the arcuate nucleus
Raun, Vrang, Jelsing, Tang-Christensen and Bjerre Knudsen.
Poster 584 at ADA 2010. Diabetes 2010;59(S1):A159.
.
42. Four criteria define what is considered a physiologically relevant satiety signal:
1. Levels must be rapidly and transiently increased by energy intake
2. Appetite suppressing effects cannot be caused only by nausea or malaise
3. Appetite suppressing effects must be observed at physiological doses
4. Blockade of the signal must increase energy intake
, YES; ×, NO; ? Data unclear or not tested
GLP-1 is classified as a ‘true’ satiety
signal
Criteria
Hormone 1 2 3 4
CCK
GLP-1
OXM ? (?)
PYY (?) ×
PP (?) ? ?
Amylin ? (?)
Leptin × ? ×(?)
Woods. Physiol Behav 2005;86:709–16
CCK, cholecystokinin; GLP-1, glucagon-like peptide-1; OXM, oxyntomodulin; PP, pancreatic polypeptide; PYY, peptide YY
43. • The effects of GLP-1 on appetite and
energy intake are mediated via:
1. GLP-1 secreted from the gut that
signals the brain through GLP-1R
activation on vagal afferents; or
2. GLP-1 secreted and released in brain
that activates the GLP-1R in specific
appetite centres
GLP-1 effects on appetite and energy intake
may be mediated via the brain–gut axis
Simpson et al. Expert Rev Endocrinol Metab 2008;3:577–92; Cooke & Bloom. Nature Reviews Drug Discovery 2006;5:919–31
Vagus nerve
GLP-1
GLP-1
GLP-1R, glucagon-like peptide-1 receptor
44. Agenda
• Historical perspective
• Brain control of glucose homeostasis
• Brain centerd glucoregulatory system BCGS.
• Glucose effectiveness.
• Dysfunction in the BCGS.
• Conclusion
.
50. The mechanism underlying metabolic benefit conferred by bariatric procedures is
incompletely understood but may involve improvements of both islet- and brain-
centred glucoregulatory systems.
A study in a model of bariatric surgery (‘duodenal exclusion’) showed that blood
glucose levels could be normalized in diabetic rats via insulin-independent activation
of a neural circuit that inhibits HGP.
Although mechanisms underlying BCGS activation by bariatric surgery await further
study, recent evidence offers a link between enhanced secretion of FGF19, the
nervous system and the gastrointestinal tract.
51. Conclusions
• Normal glucose homeostasis depends on cooperation
between the brain-centered glucoregulatory system (BCGS) and
the islet-centered system. Damage to either side of the system
initiates secondary damage to both sides. Glucose
intolerance develops after both systems are compromised.
• l BCGS model : Increasing postprandial levels of GLP-1, FGF19,
insulin, and glucose activate the BCGS, which, in turn, stimulates
both insulin-dependent and insulin-independent mechanisms that
coordinate with islet cell functioning to maintain homeostasis.
• Islet-centered model: Increased postprandial blood glucose
levels stimulate islet cells to release insulin, which acts on the
liver to decrease hepatic glucose production and on adipose and
muscle tissues to increase glucose uptake.
52. Conclusion
Looking to the future, there are several important fundamental
questions to address before the broader scientific community
can (or should) be expected to embrace a role for the brain
comparable to that of the islet in the day-to-day control of
blood glucose levels.
Studies are needed to determine whether the maintenance of
normal GE, which is known to be required for normal glucose
tolerance, is dependent on a properly functioning BCGS ?
A related and equally important question is whether the link
between reduced GE and the development of T2D is explained
by BCGS dysfunction ?
Such findings would offer direct evidence that failure of
both the BCGS and the islet is integral to diabetes
pathogenesis.