Diabetes Mellitus 1. Pancreas a.

Functionally, has two parts: the exocrine acinar cells and the endocrine islets of Langerhans b. Acinar cells produce enzymes that enter the GI tract c. Beta cells secrete insulin, insulin bind to tyrosine kinase receptors i. Regulation of insulin 1. d. Alpha cells secrete glucagon, glucagon binds to GPCRs cascade ends in the activation of glycogen phosphorylase for glycogenolysis and glucose-6-phosphatase for gluconeogenesis. i. Regulation of glucagon 1. Stimulated by hypoglycemia, epinephrine, arginine, alanine, acetylcholine, cholecystokinin 2. Inhibited by somatostatin, insulin, increased FFA and ketoacids in blood, increased urea production e. Beta cells sensitive to epinephrine, acetylcholine, and somatostatin 2. Insulin and glucagon a. Negative feedback loop b. Increase glucose levels to insulin release pathway i. Increase plasma glucose levels ii. Increase intracellular glucose in beta cells (GLUT2) iii. Glucose to ATP iv. ATP increase leads to closure of K+ channels v. Increase intracellular calcium vi. Insulin release c. Insulin to glucose uptake pathway i. Insulin bind to tyrosine kinase receptors of hepatocytes and skeletal myocytes ii. Cascade that ends in up-regulation of GLUT4 iii. Glucose uptake 3. Diabetes (polyuria) Mellitus (sweet) a. IDDM i. Destruction of beta cells (apoptosis) ii. Insulin prohormone is not cleaved into insulin and C peptide (receptor site is blocked) b. T2DM i. Insulin insufficiency ii. Insulin resistance 4. Symptoms a. Polyuria, polyphagia, polydipsia b. Hyperglycemia, Glycosuria due to osmotic diuresis

c. Hyperglycemia: poor blood circulation, poor wound healing, neuropathy, foot ulcers, necrosis, amputations 5. Diagnosis a. OGTT b. FOG c. C-peptide test to distinguish type 1 from 2 i. Low levels type I ii. Normal to elevated type II 6. Treatment a. IDDM i. Insulin (titration) b. NIDDM i. Metformin (suppress gluconeogenesis) ii. Sulfonylureas (block K+ channels) iii. Insulin 7. Diabetic ketoacidosis a. Insulin Deficiency hyperglycemia and lipolysis b. Hyperglycemia glycosuria and polyuria by osmotic diuresis c. Lipolysis ketone bodies electrolyte imbalance