Regulating blood sugar

The Pancreas Medline Plus © 2008 Paul Billiet ODWSODWS

Anatomy The pancreas is an exocrine gland secreting alkaline digestive juices into the duodenum via the pancreatic duct The pancreas is also an endocrine gland the endocrine cells are in the Islets of Langerhans © 2008 Paul Billiet ODWSODWS

Islets of Langerhans An oval collection of cells scattered through the pancreas 1 to 2 million islets in a human pancreas 1 to 2% of its mass Islets are darker red than the surrounding tissue having a rich blood supply The blood from the islets drains into the Hepatic Portal Vein going directly to the liver © 2008 Paul Billiet ODWSODWS

Hormone secreting cells  cells. (20%) secrete glucagon  cells (75%) secrete insulin  cells (1 to 8%) © 2008 Paul Billiet ODWSODWS

Insulin and Glucagon INSULINGLUCAGON A protein made of two short polypeptide chains linked by disulphide bridges Synthesised at the ribosome on Rough ER) as a single polypeptide (proinsulin) It is later activated by enzymatic cleavage into the two chains. A small protein made up of 29 amino acids It is made by the alpha cells in the Islets. It is also made in an inactive form proglucagon before it is released © 2008 Paul Billiet ODWSODWS

Hormone action Action of InsulinAction of Glucagon Increases the entry of glucose into the body cells Inhibits glycogen breakdown in liver and muscle Glucagon binds to liver cells, stimulating the breakdown of glycogen into glucose Inhibits lipid breakdown in liver and adipose tissue Increases lipid breakdown though its influence is small Increases the uptake of amino acids by cells and increases the rate of protein synthesis Stimulates the formation of glucose from amino acids in the liver © 2008 Paul Billiet ODWSODWS

Hormone action Action of InsulinAction of Glucagon The action of insulin is very rapid, so is its breakdown (t ½ = 10 to 25 min). Once released into the blood stream insulin binds with the receptor sites on its target cells’ plasma membrane. This stimulates vesicles, which carrying glucose pores, in the cytoplasm of these cells, to fuse with the plasma membrane. Insulin is broken down by enzyme action in many tissues. Glucagon is also very short lived (t ½ = 5 to 10 min). Glucagon is broken down particularly by the liver tissue. As the hormone is secreted into the blood flowing into the liver little glucagon is seen circulating in the rest of the body. © 2008 Paul Billiet ODWSODWS

Control Control of Insulin SecretionControl of Glucagon Secretion Because it has a rapid half-life the islet cells tend to respond more often to stimulating rather than inhibiting chemicals in the plasma. These include: Glucose, amino acids, glucagon, Glucagon levels rise between meals as the glucose and fatty acid levels in the blood fall Secretion is also stimulated by amino acids and hormones secreted by the digestive system In many ways it is antagonistic to insulin. © 2008 Paul Billiet ODWSODWS

Summary INSULIN GLUCAGON Normal blood glucose concentration © 2008 Paul Billiet ODWSODWS

INSULIN DEFICIENCY: Diabetes mellitus Symptoms Hyperglycaemia (high blood glucose) Glucosuria (glucose in the urine) Polyuria (passage of copious urine) Polydipsia (drinking large amounts) Increased appetite Weight loss Acids and ketones in the blood from lipid breakdown (toxic) Coma if ketones build, up © 2008 Paul Billiet ODWSODWS

Diabetes Diabetes is sometimes described as: “STARVATION IN THE MIDST OF PLENTY” There is plenty of glucose circulating in the blood but it cannot get into the cells that need it Treatment Intravenous or oral doses of insulin at regular intervals Strict diet and meal times © 2008 Paul Billiet ODWSODWS

Types of diabetes Type 1 Aka “Juvenile” Type 2 Aka “adult-onset” β-cells no longer make insulin Insulin made normally but the body cells do not use it Islet cells destroyed by the immune system (autoimmune disease) More insulin is secreted to compensate Eventually the islet cells cannot keep up with the demand © 2008 Paul Billiet ODWSODWS

Types of diabetes Type 1Type 2 Thought to be genetic in origin Associated with obesity and inactivity May be triggered by childhood infection (e.g. mumps) Obseity also has a genetic predisposition Today more and more young people suffer from Type 2 © 2008 Paul Billiet ODWSODWS

Gestational diabetes Similar to Type 2 Develops during pregnancy Placental hormones interact with insulin secretion Women who develop it seem to have a genetic predisposition © 2008 Paul Billiet ODWSODWS

Increasing numbers of diabetics Life style (exercise, snacking) Change of diet (refined sugar, saturated fats) Migration and change of diet Ethnic differences (US: Caucasians 6%, Afro/Asiatic Americans 10%, Native Americans 20-50%) © 2008 Paul Billiet ODWSODWS