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
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.
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
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
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.
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
Hormones of pancreas (The Guyton and Hall physiology Maryam Fida (o-1827))Maryam Fida
Pancreas is composed of two major types of tissues.
1. The Acini: which secrete digestive juices into the duodenum.
2. The islets of Langerhans: Contain three major types of cells INSULINMetabolized by the enzyme Insulinase (present mainly in the liver, kidneys and muscles).
Insulin is a small protein, it is composed of two amino acid chains connected to each otherby disulfide linkages. When the two amino acid chainsare split apart, the functional activity of the insulinmolecule is lost.
Insulin is synthesized in the beta cells.
Diabetes Mellitus
Hormones of pancreas (The Guyton and Hall physiology Maryam Fida (o-1827))Maryam Fida
Pancreas is composed of two major types of tissues.
1. The Acini: which secrete digestive juices into the duodenum.
2. The islets of Langerhans: Contain three major types of cells INSULINMetabolized by the enzyme Insulinase (present mainly in the liver, kidneys and muscles).
Insulin is a small protein, it is composed of two amino acid chains connected to each otherby disulfide linkages. When the two amino acid chainsare split apart, the functional activity of the insulinmolecule is lost.
Insulin is synthesized in the beta cells.
Diabetes Mellitus
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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2. ANTIDIABETIC DRUGS
Classification and the nomenclature of diabetes mellitus (DM):
DM is a chronic metabolic disorder characterised by a high blood glucose
concentration-hyperglycemia (fasting plasma glucose > 7.0 mmol//L, or plasma
glucose > 11.1 mmol/L 2hr after a meal) - caused by insulin deficiency, often combined
with insulin resistance. Hyperglycemia occurs because of uncontrolled hepatic glucose
output and reduced uptake of glucose by skeletal muscle with reduced glycogen
synthesis. When the renal threshold for glucose reabsorption is exceeded, glucose
spills over into the urine -glycosuria and causes an osmotic diuresis - polyuria, which in
turn, results in dehydration, thirst and increased drinking – polydipsia.
Diabetic ketoacidosis is an acute emergency- it develops because of accelerated fat
breakdown to acetyl-CoA, which, in the absence of aerobic carbohydrate metabolism,
is converted to acetoacetate and beta-hydroxybutyrate (which cause acidosis) and
acetone (a ketone)
3. ANTIDIABETIC DRUGS
Various complications develop as a consequence of the metabolic
derangements in DM, often over many years
Many of these are the results of disease of blood vessels, either large (macrovascular
disease) of small (microangiopathy).
Macrovascular disease consists of acclerated atheroma, which is much more
common and severe in diabetic patients.
Microangiopathy particularly affects the retina (blindness), kidney (chronic renal
failure) and peripheral nerves (diabetic neuropathy,which is associated with
accumulation of osmotically active metabolites of glucose.
Coexisting hypertension promotes progressive renal damage.
4. ANTIDIABETIC DRUGS
Classification and the nomenclature of diabetes mellitus (DM):
Type 1 diabetes encompasses cases resulting from
pancreatic B cell destruction (immune-mediated in
most cases).
Type 2 diabetes consists of combined defects of
insulin secretion and action ranging from
predominantly insulin resistance with relative insulin
deficiency to a predominantly secretory defect with
insulin resistance.
5. ANTIDIABETIC DRUGS
Type 1 diabetes (DM1) is a severe form associated with ketosis in the
untreated state. It occurs most commonly in juveniles but occasionaly in adults, the
nonobese. It is a catabolic disorder form in which circulating insulin is virtually absent,
plasma glucagon elevated, and the pancreatic B cells fail to respond to insulinogenic
stimuli (Fig.1).
Type 2 diabetes (DM2) represents a heterogenous group comprising
milder forms of DM that occur predominantly in adults. Circulating endogenous
insulin is often subnormal or relatively inadequate because of tissue insensitivity.
Obesity, which generally results in impaired insulin action, is a common risk factor, and
most patients with DM2 are obese. In addition to tissue insensitivity to insulin, there is
an accompanying deficiency of the pancreatic B cells´s response to glucose (Fig.2).
6. Fig. 1. Schematic diagram of two-phase release of insulin in response to a
constant glucose infusion
glucose
prediabetes/diabetes
Type 2
normal
Basal
level
early phase late phase
Type 1
permitted
Arb.
units
7. ANTIDIABETIC DRUGS
INSULIN (I)
is a small protein which contains two chains (A and B) linked by disulfide bridges. I is
released from pancreatic B cells at a low basal rate and at much higher stimulated rate
in response to a variety of stimuli, especially glucose.
Degradation The liver and kidney are the two main organs that remove I from the
circulation, presumably by hydrolysis of the disulfide connection between the A and B
chains through insulinase. Further degradation by proteolysis occurs. The liver normally
clears the blood of approximately 60% of the insulin released from the pancreas as the
terminal of portal vein blood flow, with the kidney removing 35-40% of the
endogenous hormone. In contrast, in insulin-treated diabetics receiving s.c. I , this ratio
is reversed.
8. ANTIDIABETIC DRUGS
The insulin receptor
Once I has entered the circulation, it is bound by specialised receptors identified in
only a few target tissues (e.g. liver, muscle and adipose tissue
(Fig. 1) The full insulin receptor consists of two heterodimers, each containing an alpha
subunit, which is entirely extracellular and constitues the recongition site, and a beta
subunit, which spans the membrane.The beta subunit contains a tyrosine kinase. When
insulin binds to alpha subunit at the outside surface of the cells, tyrosine kinase activity
is stimulated in the beta portion (nine substances have been identified for the
activated insulin receptors to be phosphorylated). Self-phosphorylation of the beta
portion results in translocation of certain proteins such as glucose transporter from
sequestered sites within adipocytes and muscle cells to exposed locations on the cell
surface. Finally, the insulin-receptor complex is internalised.
9. Fig. 2.
INSULIN RECEPTOR
Binding sites
Cell
membrane
Tyrosin kinase
Intracellular
space
Schematic diagram of the two-phase release of insulin
in response to a constant glucose infusion.
10. ANTIDIABETIC DRUGS
Schematic diagram of the two-phase release of insulin in response to a
constant glucose infusion (Fig. 2).
The first phase is missing in DM2 and both are missing in DM1. In contrast, it is
produced by aminoacids, glucagon, gastrointestinal tract hormones (gastrin,
secretin), which are released by eating. Other stimuli include fatty acids, the
parasympathetic nervous system stimulation, and drugs that act on
sulfonylurea receptors.
Insulin release is inhibited by the sympathetic nervous system (the role of
alpha2adrenoceptors) and several peptides (somatostatin)
Downregulation of insulin receptors: appears in clinical situation associated with
elevated blood levels, such as obesity of insulinoma.
11. ANTIDIABETIC DRUGS
Effects of insulin (I) on its targets
I promotes the storage of fat as well as glucose (both sources of energy) within
specialised target cells and influences cell growth and metabolic functions of a wide
variety of tissues.
1.Action of insulin on glucose transporters
I has an important effect on several transport molecules that
facilitate glucose movement across cell membranes (GLUT 1-GLUT 4)
GLUT-4 (inserted into the membranes of muscle and adipose cells) is
responsible for insulin-mediated uptake of glucose
GLUT-2 (B-cells of pancreas) mediates transport of glucose into pancreatic B-
cells. Its defects may contribute to the reduced insulin secretion that
characterizes DM2
12. ANTIDIABETIC DRUGS
2. Action of insulin on liver
The first major organ reached by endogenous insulin via portal circulation in the liver,
where it acts to:
increase storage of glucose and to
reset the liver to the fed state
by reversing a number of catabolic mechanisms associated with the postabsorptive
state:glycogenolysis, ketogenesis, and gluconeogenesis
These effects are brought about directly through activation or repression of selective
enzymes or indirectly by reducing fatty acids flux to the liver via antilipolytic action on
adipocytes.
In addition I decreases urea production, protein catabolism, promotes triglycerides
synthesis, and increases potassium and phosphate uptake by the organ.
13. ANTIDIABETIC DRUGS
3. Effect of insulin on muscle
promotes protein synthesis by increasing amino acid transport and by stimulating
ribosomal activity. It also promotes glycogen synthesis to replace glycogen stores
expended by muscle activity.
4. Effect of insulin on adipose tissue
I acts to reduce circulating free fatty acids and to promote triglyceride storage in
adipocytes (the most efficient means of storing energy).
14. Treatment of DM
Insulin is essential for the treatment of DM1
Diet is the cornestone, combined with increased
exercise
15. Pharmacokinetics
Insulin is destroyed in the GIT, and must be given parenterally (s.c., i.v., i.m.).
Pulmonary absorption occurs and inhalation of
an aerosol is a new route of administration. Once absorbed, insulin has an elimination
half-life of approximately 10 min, it is inactivated enzymatically in the liver and kidney
Species of insulin
Beef (slightly more antigenic) and purified monospecies pork
insulin. Declining costs for biosynthesis of human insulin generally
supplanted purified pork insulins.
H u m a n i n s u l i n s are produced by recombinant DNA techniques – by inserting
the human proinsulin gene into E. coli or yeast and treating the extracted proinsulin to
form the human insulin molecule. Human insulin from E.coli is available for clinical use
as Humulin and dispensed as either regular, NPH, lente or ultralente Humulin.
16. Insulin
Various formulations of insulin are available, varying in the timing of
their peak affect and duration of action (Fig. 3).
ultra-short acting insulin- Insulin lispro
monomeric insulin produced by recombinant technology, in which two aminoacids
(proline and lysine) have been reversed in their position without any influence on
receptor binding.
The advantage is quick dissociation into monomers and rapid absorption. Peak serum
value is reached in 1 hr. Its use is associated with significantly improved glycemic
control (without increasee incidence of hypoglycemia).
Used for emergency (ketoacidosis), for rapid response
(surgery).
Insulin analogues - alteration of the insulin peptide provides an
opportunity to change the absorption rate of the molecule. Insulin lispro (ultra-short
acting insulin) and
glargine ultra-long acting insulin are the first to use.
17. Insulin
short - acting insulin regular insulin (HM-R),
soluble crystalline zinc insulin, the only type of insulin that should be
administered i.v.
intermediate - acting and long- acting insulin
are made by precipitating insulin with protamine or zink, thus forming finely divided
amorphous solid or relatively insoluble crystals, which are injected as a suspension
from which insulin is slowly absorbed. These preparations include isophane insulin and
amorphous or crystalline insulin zinc suspension.
NEPHAN INSULIN (NPH, neutral protamine or isophane insulin) is an
intermediate insulin with the delayed onset of action achieved by combining
appropriate amount of insulin and protamine.
18. Insulin
LENTE INSULIN is a mixture of 30% semilente - an amorphous precipitate of
insulin with zinc ions in acetate buffer that has a relatively rapid onset of
action + 70% of ultralente insulin.
ULTRALENTE INSULIN –HUMULIN ULTRALENTE –
a poorly soluble crystal zinc insulin that has a delayed onset and prolonged
duration of action.
This is needed in type1 patients to achieve basal insulin concentratin
throughout the 24 hrs that are comparable to those achieved in normal
subjects by basal endogenous secretion.
GLARGINE – soluble, peakless, ultra-long acting insulin.
The attachment of two arginine molecules to the chain B and substitution of a
glycine for asparagine created an analogue, which precipitates after s.c.
injection
the crystalline depot to provide a peakless basal insulin
replacement that can last more than 24 hours.
21. Insulin
INSULIN DELIVERY SYSTEMS
Insulin pen injectors: to facilitate multiple s.c. injections of insulin,
portable pen-sized injectors have been developed. These contain replaceable
cartridges of U100 human insulin and retractable needles. Disponsable insulin pens are
also available for regular insulin, insulin lispro, NPH insulin. Pens eliminate the need
to carry syringes and bottles of insulin to the workplace and while traveling.
Continuous subcutaneous insulin infusion device
(insulin pumps): the devices have a manually programmable pump that
delivers individualized basal and bolus insulin replacement based on blood glucose
self-monitoring results.Normally, the 24hours basal rates are relatively constant from
day to day, though temporarily altered rates can be superimposed to adjust for a
short-term change in requirement. It is usually placed on a belt or in a pocket , and the
insulin is infused through thin plastic tubing that is connected
22. Insulin
INSULIN DELIVERY SYSTEMS (to continue)
to the subcutaneously inserted infusion set. The insulin reservoir, tubing, and infusion
set need to be changed using sterile techiques every 2 or 3 days. The use is
encouraged for individuals who are unable to obtain target control while on multiple
injection regimens and in circumstances where excellent glycemic control is desired
(pregnancy). A regular insulin is the only insulin specifically approved for pump use.
Inhaled insulin
has a rapid onset and a relatively short duration of action. It should be used to cover
mealtime insulin requirements or to correct high glucose levels.
24. Insulin
Adverse effects:
- hypoglycemia
common and, if severe, can cause brain damage. Warning signals of more rapid
development due to regular insulin:tachycardia, palpitations, sweating, tremulousness
(the sympathetic nerv syst. hyperactivity)
+ nauzea, hunger --convulsions + coma (parasympathetic hyperactivity).
In older diabetics, in those taking longer-acting insulins, are mainly symptoms of
impaired function of the CNS : mental confusion, bizarre behavior, ultimately coma
The treatment is to take a sweet drink or snack, or, if the patient is unconscious, to
give i.v. glucose or i.m. glucagon.
- allergy is unusual but can occur as local or systemic reactions
25. Insulin
Clinical uses of insulin:
- patients with DM1 require long-term maintenance treatment with
insulin. An intermediate-acting preparation is often combined
with a short-acting preparations taken before meals
- soluble insulin is used (i.v.) in emergency treatment of
hyperglycemic diabetic emergencies (ketoacidosis)
- many patients with DM2 ultimately require insulin treatement
- short-term treatment of patients with DM2 or impaired glucose
tolerance during intercurrent events (operations, infections,
myocardial infarction)
- emergency treatment of hyperkalemia: insulin is given with
glucose to lower extracellular K+ via redistribution into cells
27. ORAL HYPOGLYCEMIC AGENTS
Biguanides -Metformin
Lowers blood glucose- increases glucose uptake and utilisation in muscle + reduces
hepatic glucose production (gluconeogenesis)
Adverse effects:
- GIT disturbancies (anorexia + weight loss, diarrhea) = transient
- lactic acidosis rare but potencially fatal
Metformin should be avoided in patients who predispose to lactic acidosis (renal and
hepatic disease, heart failure…)
Use: DM2, patients obese and who fail treatment with diet alone. It does not
cause hypoglycemia
28. ORAL HYPOGLYCEMIC AGENTS
Sulfonylureas
stimulate insulin secretion by B-cells (the equivalent of phase 1- secretagogues) and
thus reducing plasma glucose.
Pharmacokinetics:
. well absorbed orally,
. all bind strongly to plasma albumin and compete for these binding
sites with salicylates and sulfonamides,
. most are excreted in the urine their action is increased in
the elderly and in patients with renal disease
. cross the placenta severe hypoglycemia at birth
s. are generally contraindicated in pregnancy
30. ORAL HYPOGLYCEMIC AGENTS
Meglitidines
A new class of insulin secretagogues modulates B cell insulin release by regulating
potassium efflux through the potassium channels
repaglinid has a very fast onset of action, with a peak concentration and peak
effect within approximately 1 hour after digestion.
31. ORAL HYPOGLYCEMIC AGENTS
Thiazolidinediones
a recently introduced class of drugs that enhance target tissue insulin sensitivity-
rosiglitazone, pioglitazone
Their main action is to diminish insulin resistance by increasing glucose uptake and
metabolism in muscle and adipose tissues.
Alpha-glucosidase inhibitors
Acarbose and miglitol are competitive inhibitors of the intestinal
enzymes and modulate the postprandial digestion and absorption of starch and
disacharides.
32. ORAL HYPOGLYCEMIC AGENTS
Clinical uses of oral hypoglycemic drugs:
-DM2 as a supplement to diet and excercise to reduce
symptoms from hyperglycemia
- metformin is preferred for obese patients unless
contraindicated by factors that predispose to lactic
acidosis
- drugs that act on the sulfonylurea receptors are well
tolerated but often promote weight gain.