The Endocrine Pancreas Chapter 15

Pancreas EXOCRINE : secretion of enzymes for food digestion ENDOCRINE: secretion of hormone for energy metabolism and fuel homeostasis in the body Fx of whole pancreas: related to the overall process of digestion, uptake and use of metabolic fuel

Pancreas contains 1 million islets. Microscopic Anatomy of the Endocrine Pancreas The endocrine pancreas consists of cells known as islets of Langerhans. Pancreas contains 1 million islets. They compose 1-2% of total mass of total mass of pancreas.

Cell types: alpha = glucagon beta = insulin delta = somatostatin Microscopic Anatomy of the Endocrine Pancreas Islets of Langerhans are numerous, small endocrine cell clusters having a rich blood supply. Beta Cell (center) Alpha Cell (rim) Cell types: alpha = glucagon beta = insulin delta = somatostatin 25% 60% Delta Cell Capillaries Fig 15-3, pg 455

Insulin has A and B chains linked by disulfide bonds. COOH COOH S S S A-chain S S S B-chain Fig 15-4, pg 456

C-peptide: index of insulin production Proinsulin  C-peptide excision  release of A-B (insulin) plus C-peptide. C-peptide: index of insulin production

Insulin Insulin-containing vesicles release insulin by exocytosis; blood insulin is mostly free.

Stimulus for Insulin secretion Glucose Plasma glucose (mg/100 ml) Blood insulin levels rise 10-30 fold soon after blood glucose exceeds 100 mg/dl. Insulin Glucose  very rapid and large increase in insulin secretion Plasma insulin (ng/ml) Fig 15-5, pg 457 Hours

Blood glucose Insulin secretion Plasma insulin Blood insulin is part of a feedback loop to maintain a constant blood glucose level. Glucose uptake into tissue Blood glucose Restoration of blood glucose to normal Fig 15-6, pg 457

Other factor that control insulin secretion Amino and fatty acids mildly stimulate insulin release. GI hormone (gastrin/secretin) stimulate insulin release; anticipatory signal Parasympathetic stimulates insulin release; sympathetic or epinephrine inhibits. Glucagon and sulfonylureas stimulate release; somatostatin inhibits.

Synthesis by alpha cells: proglucagon  glucagon

Stimulus for glucagon secretion Glucagon secretion is highest at fasting; an opposite release pattern from insulin.

Other factor that control glucagon secretion Amino acids stimulate glucagon and insulin release; blood glucose level are maintained after protein-rich meal. Fatty acids inhibit glucagon. Effect of insulin: Glucose inhibits glucagon secretion, but glucagon stays high if insulin is absent (diabetes).

Action of insulin and glucagon Two primary hormones involved in regulating fuel homeostasis in the body. With two hormones, blood glucose level is maintained within narrow limits. What for?: CNS relies almost solely on glucose for its metabolic needs. vs. high level of blood glucose  loss of water

Insulin: hormone of nutrient abundance When influx of nutrient is high, insulin directs storage of fuels, suppressing mobilization of preexisting fuel stores.

Insulin membrane receptor has tyrosine kinase activity; targets are muscle, fat, and liver. Insulin lowers blood glucose level very rapidly and effectively.

Except for brain and liver, tissues require insulin for facilitated diffusion glucose uptake. Blood Cytoplasm Insulin stimulates glycogen synthesis in liver and muscle, and glycolysis in most cells. In liver, insulin inhibits gluconeogenesis. Glycogen Liver Glycogen synthesis Glucose Glucose Gluconeogen- esis liver) Muscle and adipose Glycolysis Citric acid cycle Plasma membrane Fig 15-7, pg 461

Hormone sensitive lipase Stimulates glucose uptake, lipogenesis, and lipid uptake in adipose; inhibits lipolysis. Lipid metabolisum Glucose Glucose -Glycerol-phosphate Triacylglycerols Blood AcetylCoA Hormone sensitive lipase Fatty acid synthesis Fatty acids Liver Glycerol Lipoproteins LPLipase Adipose cell Fig 15-8, pg 461 Stimulates uptake of lipoprotein

Insulin: protein metabolism 40% of total body protein is in muscle Stimulates amino acid uptake and protein synthesis in muscle; inhibits proteolysis. In DM, net loss of protein. Blood Protein synthesis Amino acids Amino acids Protein Protein degradation Muscle Fig 15-9, pg 462

Glucagon increases blood glucose. Glucagon has opposite cellular effects from insulin; works via cAMP; liver is main target. Glucagon increases blood glucose. Glycogen 1. Glycogenolysis Glucose Glucose 2. Gluconeogenesis Blood Liver Citric acid cycle 3. Glucose sparing Fig 15-10, pg 463

Glucagon stimulates liver lipolysis and ketogenesis; heart and muscle use ketones. Glucose Glucose Liver -Glycerol-phosphate Triacylglycerols Acetyl-CoA Hormone-sensitive lipase Glucose sparing lipolysis Fatty acids Fatty acids Glycerol Ketogenesis Ketone bodies Ketone bodies Blood Fig 15-11, pg 463

Glucagon stimulates liver proteolysis, gluconeogenesis, and urea cycle. Amino acids Protein synthesis Gluconeogenesis Amino acids Glucose Protein Protein degradation Ammonia Urea synthesis Urea Liver Blood Fig 15-12, pg 464

High protein, low carbohydrate meal Both insulin and glucagon Concerted Effects High protein, low carbohydrate meal Both insulin and glucagon insulin: synthesis of protein while glucagon: maintain blood glucose level

Ex) if insulin secretion is deficient High blood glucose Concerted Effects High I/G (as high as 30) produces anabolism; low I/G (as low as 0.5) produces catabolism. Ex) if insulin secretion is deficient High blood glucose Without insulin, glucagon secretion is not inhibited. I/G ration; high extremely high blood glucose

Concerted Effects Most body energy stores are fats; fats have high caloric density and hold no water.

(c) 2003 Brooks/Cole - Thomson Learning Insulin stimulates: 1) storage of ingested carbohydrates as glycogen (liver) and fats (adipose) Protein Muscle Glycogen Liver Glucose Amino acids -Glycerol-phosphate Glycogen Fatty acids Glucose Triacylglycerols Glucose Amino acids Amino acids Fatty acids Lipo proteins Protein Glucose LPL Blood Amino acids Fatty acids -Glycerol- phosphate Protein Insulin high Glucagon low Triacylglycerols Fig 15-13, pg 466 Adipose tissue

Insulin stimulates: 2) conversion of ingested amino acids to protein (c) 2003 Brooks/Cole - Thomson Learning Protein Muscle Glycogen Liver Glucose Amino acids -Glycerol-phosphate Insulin stimulates: 2) conversion of ingested amino acids to protein Glycogen Fatty acids Glucose Triacylglycerols Glucose Amino acids Amino acids Fatty acids Lipo proteins Protein Glucose LPL Blood Amino acids Fatty acids -Glycerol- phosphate Protein Insulin high Glucagon low Triacylglycerols Fig 15-13, pg 466 Adipose tissue

Insulin stimulates: 3) conversion of ingested fatty acids to fats (c) 2003 Brooks/Cole - Thomson Learning Protein Muscle Glycogen Liver Glucose Amino acids -Glycerol-phosphate Glycogen Fatty acids Glucose Triacylglycerols Glucose Amino acids Amino acids Insulin stimulates: 3) conversion of ingested fatty acids to fats Fatty acids Lipo proteins Protein Glucose LPL Blood Amino acids Fatty acids -Glycerol- phosphate Protein Insulin high Glucagon low Triacylglycerols Fig 15-13, pg 466 Adipose tissue

(c) 2003 Brooks/Cole - Thomson Learning Muscle Low I/G stimulates: 1) liver and muscle glycogen and muscle protein to glucose Liver Glycogen Glycogen Ketones Glucose Glucose-6-phosphate Ketones Ketogenesis Gluconeogenesis Energy Glucose Urea Amino acids Amino acids Fatty acids LP Protein Blood Fatty acids Glycerol Triglycerides Insulin low Glucagon high Adipose tissue Fig 15-14, pg 467

(c) 2003 Brooks/Cole - Thomson Learning Muscle Liver Glycogen Glycogen Ketones Glucose Glucose-6-phosphate Ketones Ketogenesis Gluconeogenesis Low I/G stimulates: 2) adipose lipolysis and liver ketogenesis for glucose sparing Energy Glucose Urea Amino acids Amino acids Fatty acids LP Protein Blood Fatty acids Glycerol Triglycerides Insulin low Glucagon high Adipose tissue Fig 15-14, pg 467

High blood glucose  deficiency in insulin action Diabetes Mellitus High blood glucose  deficiency in insulin action Type 1 : inadequate insulin secretion, insulin-dependent diabetes mellitus (IDDM). Type 2 : a relative lack of response by target tissue cells to insulin, non insulin-dependent diabetes mellitus (NIDDM).

IDDM patients must receive insulin injections. Type 1 DM Low level of insulin 10% of all DM IDDM patients must receive insulin injections. . During adolescence, autoimmune beta cell loss; genetics + environment factor (maybe virus)

Type 2 DM 90% of DM patients has type 2 diabetes. Insulin-resistant tissues (adipose and muscle); genetics + obesity; Tx) Diet and losing weight Oral hypoglycemics: augmentation of insulin action in tissue.

Acute complications of diabetes Types 1 and 2: hyperglycemia  glucosuria  polyuria  dehydration Type 1 (low I/G): ketogenesis  ketoacidosis  urinary ketones + cations  electrolyte imbalance

Chronic complications of diabetes narrowing of larger vessels in brain, heart, and lower extremities  stroke, heart attack or loss of limb; microvascular lesions  nephropathy, retinopathy Peripheral neuropathy; sensory dysfunction  loss of feeling in lower limb ANS dysfunction  GI, bladder, and impotence,