Endocrine function of pancreas

Khalaf allah S khalaf allahSinnar university

College of medicine Department of physiology

Islets of langerhans Clusters of cells between acini of exocrine pancreas 150 µm diameter Consist of four types of cells: A or α cells (20%) secrete glucagon B or β cells (75%) secrete insulin D or γ cells (3-5%) secrete somatostatin F or δ (< 2%) secrete pancreatic polypeptide (PP)

Insulin

Insulin Control blood glucose level, storage and utilization of

glucose 5 min half life Is a polypeptide (51 amino acids) consist of tow chains

connecting together by disulphide bridges; A chain (21 amino acids) B chain (30 amino acids)

Proinsulin consist of C chain removed before insulin secretion

Cont Secreted in pancreatic veins portal veins

liver (half is bound) circulate in blood Enter cells by penocytosis and degraded in al most all

cells by proteolytic enzymes

Reg of insulin secretion Secretion is increased after food intake Glucose is main stimulus act via entering B cells and

increase intracellular Ca2+ Amino acids in diet strongly stimulate insulin secretion Parasympathetic stimulate it while sympathetic inhibit

it via α receptors

Cont GIT hormones (glucagon, gastrin, secretin and gastric

inhibitory peptide GIP) High level of ketoacids stimulate insulin secretion Somatostatin inhibit secretion of insulin Thiazide diuretics inhibit it secretion

Insulin action

Insulin action The insulin receptor is a tyrosine kinase enzyme After glucose enters a cell, insulin binding triggers

enzymatic activity that: Catalyzes the oxidation of glucose for ATP

production Polymerizes glucose to form glycogen Converts glucose to fat (particularly in adipose

tissue)

Carbohydrate metabolism Hypoglycaemic effect via:

Facilitate glucose uptake by increasing glucose transporters (GLUT)

Increase glycogen synthesis in liver and skeletal muscles

Decrease glucose output from the liver by increase glycogen synthesis and decreasing gluconeogenesis

Increase glucose utilization by skeletal muscles and adipose tissues

Cont Glucose transport in skeletal muscles and adipose

tissues depend on insulin some tissues such as liver, brain, kidneys and RBCs do

not require insulin for glucose uptake

Insulin inactivates liver phosphorylase, the principal enzyme that causes liver glycogen to split into glucose

Insulin causes enhanced uptake of glucose from the blood by the liver cells by increasing the activity of the enzyme glucokinase, which is one of the enzymes that causes the initial phosphorylation of glucose after it diffuses into the liver cells

Insulin also increases the activities of the enzymes that promote glycogen synthesis, including especially glycogen synthase

Insulin effects in liver

Protein metabolism Has anabolic effect Increase uptake of amino acid by cells (liver and

skeletal muscles) Increase rate of protein synthesis (liver and skeletal

muscles) Decrease protein catabolism

Fat metabolism Anabolic effects Increase FFAs synthesis in adipose tissues Inhibit FFAs mobilization from adipose tissues Increase synthesis of glycerol phosphate Increase formation and deposition of triacylglycerols Decrease of ketogenesis in liver and enhance uptake of them

by skeletal muscles Inhibit lipoprotein lipase ( triacylglycerol FFAs &

glycerol)

Electrolytes Increase K+ up take by increasing Na+-K+ pump

Diabetes Mellitus (DM) Results from hyposecretion or hypoactivity of insulin The three cardinal signs of DM are:

Polyuria – huge urine output Polydipsia – excessive thirst Polyphagia – excessive hunger and food

consumption Hyperinsulinism – excessive insulin secretion, resulting

in hypoglycemia

Glucagon

Chemistry Is a polypeptide (29 amino acids) 3-6 half life Is removed and degraded in liver and kidneys

Control of secretion Is mainly by blood glucose level

Hypoglycemia stimulate it secretion Hyperglycemia inhibit its secretion

Ingestion of protein and amino acids stimulate it secretion

Sympathetic nerves stimulate it via β receptors Exercise, trauma, pain, infection stimulate it secretion Somatostatin inhibit it secretion Secretin and insulin inhibit it Parasympathetic inhibit it secretion

Action of glucagon

CHO metabolism Regulate blood glucose Generally, has an opposite effects to those of insulin Increase blood glucose by;

cAMP glycogen phosphorylase glycogenolysis in liver not in muscles

Protein metabolism Protein breakdown in muscles Protein synthesis in liver Gluconeogenesis from some amino acids

Fat metabolism Fat mobilization via cAMP FFAs

ketogenesis Triglycerol synthesis and output from liver

Somatostatin

Somatostatin Polypeptide 41 amino acids Inhibit insulin and glucagon secretion