Transcript 5. Pancreas
5. Pancreas • has both exocrine (acini secrete digestive enzymes) and endocrine function (islets of Langerhans) • control: responds to blood glucose levels (humoral) • hormones are polypeptides (proteins) http://www.usc.edu/hsc/dental/ghisto/end/c_49.html 5. Pancreas • major cell types – alpha cells secrete glucagon – beta cells secrete insulin – delta cells secrete somatostatin (which inhibits insulin and glucagon secretion, and decrease fat absorption in intestines) – F cells regulate exocrine function of pancreas (secrete pancreatic polypeptide) 5. Pancreas: Glucagon • actions: hyperglycemic (increases blood glucose) – stimulates formation and release of glucose from liver (main target) • glycogenolysis - breakdown of glycogen (storage form of glucose) • gluconeogenesis - formation of glucose from noncarbohydrate molecules (e.g., amino acids, glycerol, lactic acid) – stimulates glycogenolysis in skeletal muscle – stimulates triglyceride breakdown in adipose tissue (fat mobilization) 5. Pancreas: Glucagon • control: – secreted in response to low blood sugar, rising amino acid levels in blood – inhibited by increased blood glucose and by somatostatin 5. Pancreas: Insulin • actions: hypoglycemic (lowers blood glucose) – increases transport of glucose into muscle and fat cells (NOTE: does not increase uptake by brain, liver, or kidney) – inhibits breakdown of glycogen and formation of glucose from amino acids or fatty acids (inhibits glycogenolysis and gluconeogenesis) – promotes formation of glycogen (liver, skeletal muscles), protein synthesis (muscle), and fat synthesis and storage (adipose) 5. Pancreas: Insulin (Control) • stimulated by: – increased blood glucose – increased blood amino acid and fatty acid levels – parasympathetic impulses – hyperglycemic hormones (GH, glucagon, epinephrine, thyroxine, glucocorticoids) indirectly result in insulin secretion by increasing blood glucose levels • inhibited by: – low blood glucose and by somatostatin – sympathetic impulses 5. Pancreas: Insulin - Disorders: Diabetes Mellitus (DM) • hyposecretion (or hypoactivity) of insulin • body cells not stimulated to take up glucose • hyperglycemia (excess blood glucose) – very high glucose --> nausea --> fight-or-flight response --> secretion of hyperglycemic hormones (epi, NE [adrenal medulla], glucocorticoids [adrenal cortex]) --> stimulates gluconeogenesis, lipolysis, glycogenolysis --> adds to already high glucose – not all sugar reabsorbed from urine --> glucose lost in urine (glucosuria) --> increased water loss --> excessive urine production (polyuria) and excessive thirst (polydipsia) 5. Pancreas: Insulin - Diabetes Mellitus • cells use fats as energy source (due to poor glucose uptake) • hyperglycemic hormones stimulate fat mobilization --> fats in blood (lipidemia) --> increase in lipid metabolites in blood (ketone bodies, which are strong organic acids) --> decrease blood pH (ketoacidosis) and ketone bodies in urine (ketonuria) – decreased blood pH --> severe depression of nervous system --> deep breathing --> diabetic coma --> death • polyphagia (excessive hunger) - final sign, due to use of fats and proteins as energy sources Type I Diabetes mellitus • also called insulin-dependent diabetes (IDDM; formerly juvenile onset diabetes) • onset is sudden, usually before age 15 • may be due to autoimmune attack of proteins in beta cells result is lack of insulin activity • lipidemia (high blood lipid content) and increased cholesterol lead to long-term vascular problems (arteriosclerosis, strokes, heart attacks, renal shutdown, gangrene, blindness) • treated with insulin injections or pancreatic islet transplant (newer technique) Type II Diabetes Mellitus • non-insulin-dependent (NIDDM; formerly mature-onset diabetes) • usually starts after age 40 • insulin levels are normal or elevated, but peripheral tissue become less sensitive to it • 25-30% of Americans carry gene that predisposes them to NIDDM, more likely in over-weight people (~90% of cases) – adipose cells secrete tumor necrosis factor alpha that depresses production of protein needed for glucose uptake • often controllable with diet and exercise Hyperinsulinism • excess of insulin (usually from injection of excess) • causes hypoglycemia --> secretion of hyperglycemic hormones (to raise blood glucose) - low glucose to brain --> anxiety, nervousness, tremors, weakness --> eventually, disorientation, convulsions, death due to “insulin shock” • treated by providing sugar source