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22 Cards in this Set
- Front
- Back
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What are the cell types in the Pancreatic islets?
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Alpha = 20-30 %, Glucagons, located in periphery
Beta = 60-80 %, insulin, C peptide, amylin, and pancreostatin. Located in Center. Delta = 8 %, somatostatin, gastrin, located between alpha and beta PP = Pancreatic Polypeptide, located outside the islets |
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What is the chemical structure of Insulin?
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storage in the granules (along with C chain and some proinsulin) as a crystalline complex with zinc
C chain is screted equimolar amount with insulin, IS A USEFUL MARKER OF INSULIN SECRETION Proinsulin = A & B chains + C chains, connecting C chain between A and B chains 2 disulfide bonds hold the A and B chains together |
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How does Insulin respond to Hyperglycemia?
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1. Facilitates diffusion of glucose into Beta cells
2. Phosphorylation of glucose 3. Oxidation of Glucose 6 phosphate to ATP 4. increases intracellular conc. of ATP, inhibits ATP sensitive K channels 5. decreases plasma membrane permeability for K --> depolarization of plasma membrane 6. Opening of voltage gated Ca channels, influx of Ca into cells 7. Ca activates the mechanism of exocytosis of secretory vesicles hormone of plenty, facilitates uptake and storage of glucose, AA, and fats after meal Sulfonylurea drugs stimulate insulin secretion by binding to ATP-sensitive potassium channels and blocking their activity |
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What is the time course of Insulin response to Hyperglycemia?
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within seconds after binding:
-increase uptake of glucose due to incorporation of preformed glucose transporters into plasma membrane -increase uptake of AA, K+, and phosphate next 10-15 mins: -changes in states of phosphorylation of enzymes hours to several days: -changes in synthesis of new proteins due to change in rates of translation of mRNA and transcription of DNA |
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What are some stimulatory and inhibitory factors of Insulin?
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Stimulation:
-GH, cortisol, estrogens, progesterone -obesity, catecholamines (beta) -vagus, ketones -increase glucose, AA, FFA, K+ -Glucagon Inhibition: -Glucagon -Hypoglycemia -Leptin, catecholamines (alpha) -K+, Ca, Mg depletion -Pancreostatin and Somatostatin |
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What are characteristics of Insulin Receptors?
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plasma membrane catalytic receptors - intrinsic tyrosine kinase activity
located in skeletal, cardiac muscle and adipose tissue and liver heterotetramers (2 alpha, 2 Beta) joined by disulfide linkage Beta-alpha-alpha-Beta alpha chains - act as insulin binding site beta chains - intrinsic tyrosine kinase activity (suppressed by alpha) when insulin binds to alpha --> de-suppresses activity of tyrosine kinase (beta) |
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What happens when Tyrosine Kinase is activated?
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autophosphorylation of tyrosine groups
phosphorylation of insulin-receptor substrates (IRS): -rapid change in glucose and FA metabolism -translocation of glucose receptors --> glucose influx into target cells -AA, K, phosphate, Mg into cell -gene transcription which eventually leads to protein synthesis |
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Where are places where glucose transport is not dependent on Insulin?
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Nervous tissue
Kidney tubules Intestinal mucosa RBC Beta cells of pancreas and liver |
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What are some metabolic effects of Insulin?
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Protein Metabolism:
-anabolic effect (increase AA uptake [linked to Na-K pump] in muscles, but decrease in liver, increase protein synthesis, inhibition of proteolysis Lipid Metabolism: -lipogenic, antilipolytic and antiketogenic -decrease hormone sensitivity to lipase activity -inhibit lipolytic action of Adr, GH, and glucagon -inhibition of fat oxidation Antiketogenic effect: -increase use of ketoacids in peripheral tissues, lowers production of ketone bodies |
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What are Insulin's effects on growth and what happens with too much/too little?
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due to:
-anabolic effects -increase availability of energy for growth -stimulation and synthesis of growth factors (IGF-1) -transcription and mitogenic factors acts synergistically with GH (different functions, promotes cellular uptake of different sets of AA) Insulin deficiency: -fetus results in low birth weight -wasting of lean body mass Hyperinsulinemia: -increases fetal growth and high birth weight babies |
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What are some other effects of Insulin?
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Electrolyte balance:
-increase K, Mg, and phosphate uptake by muscle and liver Vasodilatory effects: -increase in NO synthesis Appetite and Food intake: -decrease food intake, suppressive action on neuropeptide Y |
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What are some basic features of Glucagon?
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polypeptide (29 AA)
structure similar to secretin Cellular action: -liver is principal target organ -cAMP second messenger system |
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What are some stimulatory and inhibitory regulators of Glucagon?
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Stimulation:
-GIT hormones, ACH, Beta adrenergic stimulators, cortisol -Hypoglycemia, AA, and decrease FFA Inhibition: -FFA, ketones -alpha adrenergic stimuators -GLP1, Hyperglycemia -Somatostatin Blood Glucose concentration is most potent factor that controls glucagon secretion |
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What are the biological effects of Glucagon?
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opposite to insulin
glycogenolytic and gluconeogenic: -increase glycogenolysis -lower glycolysis -increase gluconeogenesis acceleration of ketogenesis, glucose sparing effect increase lipolysis --> increase level of FFA and glycerol Proteolytic effect: -inhibition of protein synthesis hormone of starvation |
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What are some basic features of Somatostatin?
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polypeptide (14 AA)
general inhibitory substance: -inhibits release of both glucagon and insulin -acts as GHIH, inhibitions secretion of TSH -inhibits motility of stomach, duodenum and galbladder -inhibits secretion and absorption of GIT secretion is stimulated by: -blood glucose, AA (Leu and Arg) -FA, CCK, glucagon, Beta adrenergic and cholinergic Inhibited by: -insulin |
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What is Pancreatic Polypeptide?
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synthesized by PP cells of pancreatic islets
inhibits exocrine pancreatic secretion, slows absorption of small intestine secretion is stimulated by fasting, acute hypoglycemia, exercise, meal containing proteins |
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What are the types of Diabetes Mellitus?
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Insulin dependant: (IDDM)
-Type I -destruction of Beta cells, absolute insulin deficiency Non-Insulin-Dependent: (NIDDM): -Type II -low insulin sensitivity of target tissues, insulin resistance -relative insulin deficiency, high secretion of insulin causes exhaustion of Beta cells |
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What is Type I IDDM?
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-Juvenile onset diabetes
-accounts for 10-20 % cases -develops acutely Pathogenesis and signs: -Hyperglycemia: glucosuria causing osmotic diuresis leading to dehydration and polydypsea; Tissue injuries to blood vessels, kidneys, retina, and nerves Increase protein catabolism Increase Lipid catabolism, use of lipids for energy, ketoacidosis Hypersecretion of Glucagon, due to decrease of inhibition of insulin: -increase in glycogenolysis and gluconeogenesis in liver -lipolysis, ketogenesis, and ketoacidosis Treatment: -Long term insulin therapy, insulin-dependant |
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What is Type II NIDDM?
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maturity onset diabetes
accounts for 80-90 % of cases occurs later in life Pathogenesis and signs: -insulin resistance: lower glucose uptake and combustion of target tissues, lowering of insulin sensitivity -insulin deficiency is relative -ketoacidosis is rare treatment: -dietary treatment -exercise -sulfonylureas |
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What are the problems with metabolism with untreated DM?
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Carbohydrate metabolism:
-low insulin secretion, resistance and high glucagon leads to hyperglycemia -glycosuria, polyurea --> hypovolemia, polydipsia, hypervolemia in ECF Protein Metabolism: -loss of lean body mass, asthenia -increase urinary excretion of urea Lipid Metabolism: -hydrolysis of triglycerides -ketoacidosis, ketonuria, acetone breath |
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What happens in Hyperinsulinism?
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Hypoglycemia:
-affects brain -below 50-70 mg/dl causes nervousness, trembling, sweating -below 20-50 mg/dl inhibits CNS -can cause permanent damage of various brain structures compensatory mechanisms: -activates sympathetic nervous system to secrete hyperglycemic hormones: -epinephrine stimulates adrenal gland to increase glycogenolysis, lipolysis etc -later response: cortisol and GH, negative feeback loop to hypothalamus |
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What are some of the physiological basis of diagnosis of DM?
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Urinary Glucose level:
-no urinary glucose in healthy people Fasting Glucose level: -normal is 80-110, in DM above 115 Blood glucose level after time: -normal: 120-140 (after meal) and falls back in 2 hours -DM: above 165 and goes down after 4-6 hours |
