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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. more...

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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.

Regulation

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.

Media


Read more at Wikipedia.org


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The Effects Of Microgravity On Insulin And Glucagon Secretions
From Life Sciences & Biotechnology Update, 11/1/99

This brief (Baylor College of Medicine) paper addresses the effects of microgravity on insulin and glucogen secretions. Long-duration space flight is associated with many physiological abnormalities in astronauts. In particular, altered regulation of the hormones insulin and glucagon may contribute to metabolic disturbances, such as increased blood sugar levels, which if persistently elevated result in toxic effects. These changes are also observed in the highly prevalent disease diabetes, which affects 16 million Americans and consumes over $100 billion in annual healthcare costs. By mimicking the microgravity environment of space in the research laboratory, using a NASA- developed bioreactor, one can study the physiology of insulin and glucagon secretion, and determine if there are alterations in these cellular processes.

The original specific objectives of the project included: (1) growing cell culture of pancreatic islet beta and alpha cells that secrete insulin and glucagon respectively, in the NASA bioreactor; (2) examination of the effects of microgravity on insulin and glucagon secretion; and (3) study of molecular mechanisms of insulin and glucagon secretion if altered by microgravity.

(Order this LIFE SCIENCES & BIOTECHNOLOGY UPDATE reviewed report from InfoTeam Inc., P.O. Box 15640, Plantation, FL 33318-5640; Phone (954) 473-9560, Fax (954) 473-0544: Report No. L991128; 1998, 5 pp. Price: $69.00, prepaid. E-mail to: InfoTeamMA@aol.com)

COPYRIGHT 1999 Merton Allen Associates
COPYRIGHT 2004 Gale Group

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