Glucagon

Glucagon is a 29-amino acid polypeptide acting as an important hormone in carbohydrate metabolism. The polypeptide has a molecular weight of 3485 daltons and was discovered in 1923 by Kimball and Murlin.

Its primary structure is: NH2-His-Ser-Gln-Gly-Thr-Phe- Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser- Arg-Arg-Ala-Gln-Asp-Phe-Val-Gln-Trp-Leu- Met-Asn-Thr-COOH

History
In the 1920s, Kimball and Murlin studied pancreatic extracts and found an additional substance with hyperglycemic properties. Glucagon was sequenced in the late-1950s, but a more complete understanding of its role in physiology and disease was not established until the 1970s, when a specific radioimmunoassay was developed.

Physiology
The hormone is synthesized and secreted from alpha cells of the Islets of Langerhans, which are located in the pancreas. The alpha cells are located in the outer rim of the islet.

Stimulus for increased secretion of glucagon

 * Decreased plasma glucose
 * Increased catecholamines
 * Increased plasma amino acids (to protect from hypoglycemia if an all protein meal consumed)
 * Sympathetic nervous system

Stimulus for decreased secretion of glucagon

 * Somatostatin
 * Insulin

Function

 * Glucagon helps maintain the level of glucose in the blood by binding to specific receptors on hepatocytes, causing the liver to release glucose - stored in the form of glycogen - through a process known as glycogenolysis. As these stores become depleted, glucagon then encourages the liver to synthesize additional glucose by gluconeogenesis. This glucose is released into the bloodstream. Both of these mechanisms lead to glucose release by the liver, preventing the development of hypoglycemia.


 * Increased free fatty acids and ketoacids into the blood
 * Increased urea production

Mechanism of action

 * Acts via cAMP generation

Pathology
Abnormally-elevated levels of glucagon may be caused by pancreatic cancers such as glucagonoma, symptoms of which include necrolytic migratory erythema (NME).

Pharmacological application of glucagon
An injectable form of glucagon is essential first aid in cases of severe hypoglycemia. The glucagon is given by intramuscular injection, and quickly raises blood glucose levels. It works only if there is glycogen stored in liver cells, and it won't work again until those stores are replenished.

Glucagon has also inotropic properties. Although its use is impracticable in heart failure, it has some value in treatment of myocardial depression secondary to betablocker overdose. However there have been no clinical controlled trial on the use of glucagon. []