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ENDOCRINE PANCREAS Anatomy • Location • Pancreatic Islets (of Langerhans) – – – – Alpha cells Beta cells Delta cells F-cells Hormones Insulin • Chemistry – Protein/Peptide • 51 amino acids • 2-chains – & – 2 disulfide bridges – Proinsulin • 86 amino acid protein • C peptide • Peptidases Insulin Action Insulin Receptor • • • • • Kinase Autophosphorylation Phosphorylation of proteins Translocation of GLUT-4 Down-regulation Glucose Transporter Proteins • • • • • GLUT-1 GLUT-2 GLUT-3 GLUT-4: INSULIN REGULATED GLUT-5 Basic effect of Insulin • Promotes uptake of glucose from the blood • Promotes storage of energyproducing nutrients Effect of Insulin on the Liver • Stimulates glycogenesis • Stimulates protein synthesis • Increased production of triglycerides, cholesterol, and VLDL • Inhibits glycogenolysis • Inhibits ketogenesis • Inhibits gluconeogenesis Effect of Insulin on Skeletal Muscle • Promotes protein synthesis • Stimulates glycogen synthesis Effect of Insulin on Fat Cells • Promotes triglyceride storage Insulin Regulation • Factors that stimulate insulin secretion – High serum glucose – High serum amino acids – Enteric hormones • Factors that inhibit insulin secretion – Glucagon – Somatostatin – -adrenergic stimulation Insulin Control SERUM AMINO ACIDS SERUM GLUCOSE GUT HORMONES GLUCAGON SOMATOSTATIN -CELL PANCREATIC ISLET INSULIN -ADRENERGIC SERUM GLUCOSE GLUCOSE UPTAKE LIVER & MUSCLE Glucagon • Chemistry – 29 amino acid peptide – Proglucagon • Action – Antagonizes the action of insulin – Acts primarily on the liver – Stimulates glycogenolysis – Stimulates gluconeogenesis – Stimulates ketogenesis Glucagon Regulation SOMATOSTATIN BLOOD SUGAR BLOOD SUGAR SYMPATHETIC INNERVATION PARASYMPATHETIC INNERVATION G-I HORMONES CORTISOL PANCREAS -CELL GLUCAGON GLUCOSE LIVER & MUSCLE Somatostatin • Chemistry – 14 amino acid peptide – Prosomatostatin – G-protein linked receptor – Produced and secreted by many tissues • Action – Paracrine Factor – Inhibits insulin & glucagon secretion • Regulation Pancreatic Peptide • Chemistry – 36 amino acid peptide • Action – unknown • Regulation – Serum levels increase after a meal, but do not increase after glucose infusion – Vagotomy abolishes response to meal Glucose Homeostasis GLYCOGENOLYSIS GLUCONEOGENESIS LIVER & MUSCLE GLUCAGON ISLET -CELLS HYPERGLYCEMIC HORMONES MEALS SERUM GLUCOSE NORMAL SERUM GLUCOSE 80-120 mg/dl ISLET -CELLS INSULIN LIVER & MUSCLE SERUM GLUCOSE GLUCOSE UPTAKE METABOLIC DEMANDS
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