glucagon n : a hormone secreted by the pancreas; stimulates increases in blood sugar levels in the blood (thus opposing the action of insulin)
Glucagon is an important hormone involved in carbohydrate metabolism. Produced by the pancreas, it is released when the glucose level in the blood is low (hypoglycemia), causing the liver to convert stored glycogen into glucose and release it into the bloodstream. The action of glucagon is thus opposite to that of insulin, which instructs the body's cells to take in glucose from the blood in times of satiation.
HistoryIn the 1920s, Kimball and Murlin studied pancreatic extracts and found an additional substance with hyperglycemic properties. They described glucagon in 1923. The amino acid sequence of glucagon was described in the late-1950s. A more complete understanding of its role in physiology and disease was not established until the 1970s, when a specific radioimmunoassay was developed.
StructureGlucagon is a 29-amino acid polypeptide. Its primary structure in humans 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.
ProductionThe hormone is synthesized and secreted from alpha cells (α-cells) of the islets of Langerhans, which are located in the endocrine portion of the pancreas. In rodents, the alpha cells are located in the outer rim of the islet. Human islet structure is much less segregated, and alpha cells are distributed throughout the islet.
Regulatory mechanismIncreased secretion of glucagon is caused by:
FunctionGlucagon helps maintain the level of glucose in the blood by binding to glucagon 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. Glucagon also regulates the rate of glucose production through lipolysis.
Mechanism of actionGlucagon binds to the glucagon receptor, a G protein-coupled receptor located in the plasma membrane. The conformation change in the receptor activates G proteins, a heterotrimeric protein with α, β, and γ subunits. The subunits breakup as a result of substitution of a GDP molecule with a GTP mol, and the alpha subunit specifically activates the next enzyme in the cascade, adenylate cyclase.
Adenylate cyclase manufactures cAMP (cyclical AMP) which activates protein kinase A (cAMP-dependent protein kinase). This enzyme in turn activates phosphorylase B kinase, which in turn, phosphorylates phosphorylase B, converting into the active form called phosphorylase A. Phosphorylase A is the enzyme responsible for the release of glucose-1-phosphate from glycogen polymers.
PathologyAbnormally-elevated levels of glucagon may be caused by pancreatic tumors such as glucagonoma, symptoms of which include necrolytic migratory erythema (NME), elevated amino acids and hyperglycemia. It may occur alone or in the context of multiple endocrine neoplasia type 1.
UsesAn injectable form of glucagon is vital first aid in cases of severe hypoglycemia when the victim is unconscious or for other reasons cannot take glucose orally. The dose for an adult is typically 1 milligram, and the glucagon is given by intramuscular, intravenous or subcutaneous injection, and quickly raises blood glucose levels. Glucagon can also be administered intravenously at 0.25 - 0.5 unit.
Anecdotal evidence suggests a benefit of higher doses of glucagon in the treatment of overdose with beta blockers; the likely mechanism of action is the increase of cAMP in the myocardium, effectively bypassing the inhibitory action of the β-adrenergic second messenger system.
Glucagon acts very quickly: common side effects include headache and nausea.
Drug interactions: Glucagon interacts only with oral anticoagulants increasing the tendency to bleed.
References in pop culture
glucagon in Bosnian: Glukagon
glucagon in Bulgarian: Глюкагон
glucagon in Czech: Glukagon
glucagon in Danish: Glukagon
glucagon in German: Glucagon
glucagon in Dhivehi: ގްލޫކަގޮން
glucagon in Spanish: Glucagón
glucagon in Esperanto: Glukagono
glucagon in French: Glucagon
glucagon in Icelandic: Glúkagon
glucagon in Italian: Glucagone
glucagon in Hebrew: גלוקגון
glucagon in Pampanga: Glucagon
glucagon in Latin: Glucagon
glucagon in Lithuanian: Gliukagonas
glucagon in Macedonian: Глукагон
glucagon in Malay (macrolanguage): Glukagon
glucagon in Dutch: Glucagon
glucagon in Japanese: グルカゴン
glucagon in Norwegian: Glukagon
glucagon in Polish: Glukagon
glucagon in Portuguese: Glucagon
glucagon in Russian: Глюкагон
glucagon in Albanian: Glukagoni
glucagon in Serbian: Глукагон
glucagon in Finnish: Glukagoni
glucagon in Swedish: Glukagon
glucagon in Tamil: குளூக்கொகான்
glucagon in Turkish: Glükagon
glucagon in Chinese: 胰高血糖素