Metabolism FOOD proteins sugars fats amino acids fatty acids simple sugars (glucose) muscle proteins liver glycogen fat lipids glucose

Mammalian Pancreas Gall bladder duodenum liver Bile Duct Pancreas Pancreatic duct -Exocrine Pancreas: secretes digestive enzymes, alkaline pancreatic fluid -Endocrine Pancreas: secretes hormones that regulate carbohydrate, lipid, and protein metabolism

Endocrine Pancreas Islets of Langerhans: 4 cell types –  cells: secrete glucagon –  cells: secrete insulin –  cells: secrete somatostatin –F cells: secrete pancreatic polypeptide Islets of Langerhans Exocrine cells    capillaries

Pancreatic Hormones Insulin Glucagon Somatostatin

INSULIN Regulation of Secretion –Hyperglycemia stimulates release Glucose sensors in  cells –Gastric Inhibitory Peptide Released from cells of the small intestine Potent stimulator of insulin secretion –Somatostatin: inhibits insulin release (paracrine) –Autonomic nervous system Parasympathetic activation increases insulin release Sympathetic activation blocks insulin release Epinephrine (from adrenal) blocks insulin release

INSULIN Action at Target Tissues –Activation of insulin receptor: Increases transport of glucose, amino acids, and fatty acids into cells Glucose transporter:

INSULIN Action at Target Tissues –Activation of insulin receptor: Increases transport of glucose (glucose transporter), amino acids, and fatty acids into cells –Enhancement of anabolic pathways, decrease in catabolic pathways –Increases enzymes that activate: Glycogen formation (liver) Lipogenesis (fat) Protein Synthesis (muscle)

Pancreatic Hormones Insulin –Hypoglycemic, glycogenic, lipogenic, anabolic Glucagon Somatostatin

Glucagon Hyperglycemic (increases plasma glucose) –(one of many in the body) Actions at target cells –Liver Promotes glycogenolysis Promotes gluconeogenesis –Fat Tissue Promotes lipolysis

Pancreatic Hormones Insulin –Hypoglycemic, glycogenic, lipogenic, anabolic Glucagon –Hyperglycemic, lipolytic Somatostatin –Paracrine agent –Believed to inhibit insulin and glucagon release –Inhibits digestion through several pathways

Glucose Regulation  Insulin: decreases blood glucose levels  Glucagon: increases blood glucose levels  Somatostatin: inhibits insulin and glucagon levels (paracrine) and digestive processes

DIABETES MELLITUS Type 1—juvenile onset—insulin dependent –IDDM –Underproduction of insulin Type 2—adult onset—non-insulin dependent –NIDDM –Insulin receptor resistance –Post-receptor mechanism problem

Type 1 Diabetes Insulin Dependent: IDDM Likely results from autoimmune reaction –The body’s immune system attacks the  cells Pancreatic  markedly reduced –Symptoms only appear after ~80% loss of cells No insulin……physiological repercussions? Treatment –Insulin injections or insulin pump –Recent methods

Islet Transplantation Inside the patient Separate islets from exocrine pancreas Encapsulate islets (immune protection) Inject into liver portal vein

Type 2 Diabetes: Non-Insulin Dependent: NIDDM Accounts for 90-95% of all Diabetes cases Usually occurs in overweight individuals over 40 years of age –But ages are getting younger and younger –Associated with abdominal fat in women Target cells become resistant to insulin –insulin receptor Fewer receptors Receptors have lower affinity Receptor blocked (possibly by antibody) –Post-receptor mechanisms

Diabetes Prevelence in US % Incidence of diagnosed diabetes

2004 % of adults >20

New Cases in <20 yrs old

Type 2 Risks th leading cause of death With Type 2 diabetes –2 to 4-fold increase in heart disease related death –2-fold risk of death Type 2 associated complications –2-4 fold risk of stroke –75% of adults with Type 2 have high blood pressure –leading cause of blindness in adults aged –Leading cause of kidney failure