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Phys Spring 4 Lec 7

Pancreatic Hormones

What are the cells of the pancreas? What structure are these cells a part of? Beta cells (60%), alpha cells (25%), delta cells (10%); Islet of Langerhans
What do beta cells secrete? Insulin
What do alpha cells secrete? Glucagon
What do delta cells secrete? somatostatin
Discuss the structure of the pancreas Islets of Langerhans are supplied w/capillaries, which carry the secretions --> portal vein --> general circulation
What is the half-life on insulin in the circulation? 6 minutes
Where is insulin metabolized? Liver
Discuss the action of insulin at the insulin receptor Insulin binds to receptor --> alters internal kinase --> initiates phosphorylation cascade --> GLUT-4 glucose transporters are moved to cell surface --> glucose uptake inc w/in seconds
Discuss the 3 mechanisms of insulin resistance 1. Blockage of insulin binding to receptor; 2. Alteration of an intracellular link b/n insulin binding and the insertion of GLUT into cell membrane; Inc speed of internal degradation of the insulin-receptor complex
Discuss the 3 effects of insulin on CHO metabolism 1. Inc glucose uptake into muscle & adipose tissue; 2. Inc glucose uptake into liver; 3. Inhibit gluconeogenesis in the liver
How does insulin affect muscle glucose storage? In muscle, unused glucose is stored as glycogen. W/on insulin, muscle is almost impermeable to glucose.
TRUE or FALSE: The nervous system requires insulin for glucose transport FALSE
How is glucose stored in the liver? Stored as glycogen, and excess glucose is converted to FA
Discuss the effects of insulin on fat metabolism Increases: glucose uptake into adipose, FFA absorption into adipose, and triglyceride (TG) synthesis in the liver; Reduces lipase action in adipose
What is glucose used for in adipose? conversion of glycerol --> triglycerides
How are triglycerides (TG) transported from the liver to adipose? By VLDLs & LDLs
What are the 4 effects of insulin DEFICIENCY on fat metabolism? 1. Adipose tissue lipase is activated --> plasma FFA levels inc; 2. FFAs used for energy (normal); 3. Excess FFA inc cholesterol & TG synthesis in liver; 4. Excess FFA are broken down into acetoacetic acid --> leading to acidosis & conversion to ketones
Discuss the effects of insulin on protein metabolism Inc: transport of glucose & AAs into muscle, and action of ribosomes in protein synthesis; Dec: catabolism of proteins by lysosomes, and gluconeogenesis by liver (so AAs are available for protein synthesis)
Describe the synergy between insulin & GH Inc the rate/amount of weight gain
What are the 4 effects of insulin DEFICIENCY on protein metabolism? 1. Protein synthesis stops, catobolism of proteins inc, plasma AA levels inc; 2. Excess AAs are used for energy or gluconeogenesis; 3. Urea levels inc in urine; 4. Muscle wasting, weakness, & organ dysfxn are all severe effects of diabetes
What stimulates insulin secretion? 1. Inc plasma glucose; 2. Inc plasma AAs; 3. CCK, glucagon, incretins; 4. B-adrenergic & cholinergic stimulation
What inhibits insulin secretion? 1. Dec plasma glucose; 2. somatostatin; 3. a-adrenergic stimulation (esp. during exercise)
What is the Incretin Effect? Oral glucose induces a much greater insulin response than does the same amount of IV glucose. The GI tract secretes incretins, which inc insulin response
What is GLP-1? What is its fxn? It is an incretin - Glucagon-like intestinal peptide. It is secreted into circulation to enhance insulin secretion
How is GLP-1 made? The L cells of the GI tract produce proglucagon, which is then cut to produce GLP-1
What is the fxn of glucagon? Inc breakdown of liver glycogen & gluconeogenesis, inc rate of AA uptake into liver cells (for gluconeogenesis), and activates enzymes of gluconeogenesis
What stimulates glucagon secretion? Hypoglycemia, inc plasma AAs,and exercise
What inhibits glucagon secretion? Somatostatin, Insulin, Glucose
Relate glucagon levels to levels of plasma glucose As plasma glucose dec, glucagon inc
What stimulates somatostatin secretion? Inc blood glucose, inc plasma AAs & FFAs, inc CCK and other GI hormones
What inhibits somatostatin secretion? Secretion of insulin, glucagon, dastrin, & GH; gastric & intestinal peristalsis
What is the fxn of somatostatin? To slow down the entire digestive process
What controls glucose use in hypoglycemia? Cortisol & GH decrease glucose use by most cells
Where is most glucose stored? Liver
How are glucagon & insulin related? Inversely proportional: Insulin acts in response to high blood glucose to reduce it, and glucagon acts in response to low blood glucose to increase it
What are the effects of hypoglycemia? Headache, weakness, shaking, cold sweat, seizures, loss of consiousness, coma (glucose is required by the brain)
What are the effects of hyperglycemia? 1. Osmotic & dehydration damage to tissue --> loss of body water in urine; 2. Inc risk of heart attack, stroke, and blindness --> glycation of proteins on endothelial cell walls
Discuss Type I diabetes AKA insulin-sensitive, juvenile onset; 1. autoimmune dz d/t viral infection; 2. destruction of pacreatic B-cells; 3. Plasma insulin levels low/absent; 4. high plasma glucose
Discuss Type II diabetes AKA insulin-insensitive, adult onset; 1. Dec sensitivity of target tissue to insulin --> "insulin resistance"; 2. High plasma glucose AND insulin --> B-cells constantly responding to excess glucose
What are acute complications of untreated type I diabetes? 1. High glucose levels cause osmotic diuresis & dehydration; 2. Excess use of FA for fuel produces ketone bodies and results in metabolic acidosis; 3. w/o tx, will lead to death w/in months
What are the chronic complications of Type II and long-term type I? Ongoing & inc damage to blood vessels, peripheral nerves, eye, and kidneys, primarily as an effect of high blood glucose via glycation
What is glycation? The aldehyde group of a glucose attached to available NH2 on an AA sidechain (no enzyme required). Rearrangement follows, leaves attached glucose w/aldehyde available to attach another NH2. Cross-linking occurs --> stiffening of protein
Discuss the HbA1c test Glycation occurs in RBCs. HcA1c measures the % of glycated Hb, which is an index of the avg glucose levels during the previous few months. An HbA1c score of 6 corresponds to an avg 115mg glucose/dL
What does glycation do to blood vessels? 1. Stiffens blood vessel proteins --> dec compliance --> HTN --> local injury & atherosclerotic deposits; 2. Thickening of basement membranes of ECs --> less O2 & nutrient transport --> local necrosis & neuropathy
What does glycation do to nerve tissue? Long-lived neurons accumulate glycation damage --> peripheral neuropathy --> major cause of non-traumatic limb amputation
What does glycation do to connective tissue? Long-lasting connective tissue accumulates glycation damage
How is blindness caused by diabetes? How often does this occur? Damage to lens proteins + retinal blood vessels + neurons --> adult-onset blindness. All type I pts and most type II pts have at least some retinal damage.
Created by: hclark86



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