ll iabetes mellitus is the third leading cause lJ of death (after heart disease and cancer) in many developed countries. lt affects about 2 to 3% of the general population. The complications of diabetes affect the eye, kidney and nervous system. Diabetes is a major cause of blindness, renal failure, amputation, heart attacks and stroke. (The term diabetes, whenever used, refers to diabetes mellitus. lt should, however, be noted that diabetes insipidus is another disorder characterized by large volumes of urine excretion due to antidiuretic hormone deficiency). Diabetes mellitus is a clinical condition characterized by increased blood glucose level (hyperglycemia) due to insufficient or inefficient (incompetent) insulin. ln other words, insulin is either not produced in sufficient quantity or inefficient in its action on the target tissues. As a consequence, the blood glucose level is elevated which spills over into urine in diabetes mellitus (Creek : diabetes-a siphon or running through; mellitus-sweet). An important feature of diabetes is that the body cells are starved of glucose despite its very high concentration around i.e. scarcity in plenty. For a comprehensive understanding of diabetes, the relevant hormones, namely insulin and glucagon, homeostasis of blood glucose, besides the biochemical aspects of diabetes, are discussed in this chaoter. lnsufin is a polypeptide hormone produced by the B-cells of islets of Langerhans of pancreas. lt has profound influence on the metabolism of carbohydrate, fat and protein. Insulin is considered as anabolic hormone, as it promotes the synthesis of glycogen, triacylglycerols and proteins. This hormone has been implicated in the development of diabetes mellitus. Insulin occupies a special place in the history of biochemistry as well as medicine. Insulin was the first hormone to be isolated, purified and synthesized.Clucagon, secreted by a-cells of the pancreas, opposes the actions of insulin. lt is a polypeptide hormone composed of 29 amino acids (mol. wt. 3,500) in a single chain. Clucagon is actually synthesized as proglucagon (mol. wt. 9,000) which on sequential degradation releases active glucagon. Unlike insulin, the amino acid sequence of glucagon is the same in all mammalian species (so far studied). Clucagon has a short half-life in plasma i.e. about 5 minutes. f, ++qu[et i tr ! af q! Nle;t g€'re li€rcrr!.f idi*l The secretion of glucagon is stimulated by Iow blood glucose concentration, amino acids derived from dietary protein and low levels of epinephrine. Increased blood glucose level markedly inhibits glucagon secretion. ftiletahe;iit: ei'fe:lts oi qgir.l*;: r';nn Clucagon influences carbohydrate, lipid and protein metabolisms. In general, the effects of this hormone oppose that of insulin. 1. Effects on carbohydrate metabolism : Glucagon is the most potent hormone that enhances the blood glucose level (hyperglycemic). Primarily, glucagon acts on liver to cause increased synthesis of glucose (gluconeogenesis) and enhanced degradation of glycogen (glycogenolysis). The actions of glucagon are mediated through cyclic AMP (Chapter t3). 2. Effects on lipid metabolism : Clucagon promotes fatty acid oxidation resulting in energy production and ketone body synthesis (ketogenesis). 3. Effects on protein metabolism : Glucagon increases the amino acid uptake by liver which, in turn, promotes gluconeogenesis. Thus, glucagon lowers plasma amino acids. Meehanisrn of ;.icti*"rri #[ g{e.E$fil{g}f, Clucagon binds to the specific receptors on the plasma membrane and acts through the mediation of cyclic AMP, the second messenger. The details are given elsewhere Diabetes mellitus is a metabolic dr'sease, more appropriately adisorder of fuel metabolism. lt is mainly characterized by hyperglycemia that leads to several long term complications. Diabetes mellitus is broadly divided into 2 groups, IDDM & NIDDM.