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
Encyclopedia
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: NH
2-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. A more complete understanding of its role in physiology and disease was not established until the 1970s, when a specific radioimmunoassay was developed.
Physiology
Production
The hormone is synthesized and secreted from alpha cells of the
islet of Langerhans, which are located in the endocrine portion of the pancreas. The alpha cells are located in the outer rim of the islet.
Regulatory mechanism
Increased secretion of glucagon is caused by:
- Decreased plasma glucose
- Increased catecholamines - norepinphrine and epinephrine
- Increased plasma amino acids
- Sympathetic nervous system
- Acetylcholine
- Cholecystokinin
Decreased secretion of glucagon is caused by:
Function
Glucagon 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.
- 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 tumors such as glucagonoma, symptoms of which include necrolytic migratory erythema , elevated amino acids and hyperglycemia. It may occur alone or in the context of multiple endocrine neoplasia type 1.
Uses
An injectable form of glucagon is essential first aid in cases of severe hypoglycemia, usually in a dose of 1 milligram. The glucagon is given by intramuscular injection, and quickly raises blood glucose levels.
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 ß-adrenergic second messenger system.
Media
References
See also
