Glucagon

  • OMIM: 138030
  • UniProt: P01275
  • MGI: 95674
  • CAS Number: 9007-92-5

Glucagon ( glucagon ) is a peptide hormone whose main task is to increase the blood sugar level. It is formed from the precursors Präglucagon and preproglucagon in the islets of Langerhans of the pancreas ( α - islet cells ). When blood sugar drop, but even after a high protein meal glucagon is released by the pancreas into the bloodstream and transported freely there. This hormone is in its effect on the glucose, protein and fatty acid metabolism an antagonist of insulin. Glucagon is taken up by the liver and inactivated by cleavage.

Structure

The primary structure of human glucagon is composed of 29 amino acids with a molecular mass of 3483 Da. The primary structure is: 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.

Glucagon secretion

A normal diet, the secretion of glucagon, when compared to the insulin remains relatively constant. The stimuli for increased distribution are mainly hypoglycemia (low blood sugar), protein-rich meals, infusion of amino acids (eg, arginine, alanine), prolonged heavy physical work and stress. When hypoglycemia glucagon secretion can be increased to up to four times. Stimulation occurs by β - adrenergic receptors. Its release is inhibited by insulin, somatostatin, and GLP-1.

Mechanism of action

Glucagon is the antagonist to insulin. While insulin promotes glycogen synthesis, the release of glucagon results in a breakdown of glycogen. The action of glucagon is based on binding to a G -protein coupled receptor. The thus activated Gs protein stimulates adenylate cyclase ( EC 4.6.1.1 ). CAMP by the enzymes for the glucose and lipid metabolism to be activated. As a priority effect glycogen phosphorylase ( EC 2.4.1.1 ) is phosphorylated, which stimulates glycogen breakdown and inhibits glycogen synthesis.

Glucagon stimulates not only the glycogenolysis, but also the de novo synthesis of glucose ( gluconeogenesis ) from amino acids. Thus, glucagon is a proteinkatabole effect, which leads to an increase in the blood of urea. In addition to cAMP amounts of fat enzymes (lipases ) are activated, resulting in an increase of fatty acids results in the blood.

Application

Glucagon is used for the immobilization of the intestine and is used in this function as intravenous medication. As an antidote for poisoning with beta-blockers and calcium channel blockers, the drug is also applied. It is also used for stomach X-ray to assess the mucosa better.

In addition, many patients with type 1 diabetes have an emergency kit with glucagon and a solvent is injected at a severe hypoglycemia with unconsciousness after dissolution of the powder substance from a trained helper subcutaneously or intramuscularly and to achieve an increase in blood sugar levels through the mechanism described above. Glucagon is sold by the manufacturer Novo Nordisk under the tradename GlucaGen ®.

For a study carried out in 2010 an insulin pump was developed, which included a Glucagonampulle next to the insulin vial. Through a continuous glucose measurement in a closed-loop system (blood glucose monitoring and dose delivery done automatically ) was delivered at Unterzuckerungsgefahr glucagon on the pump. This occurred less and less persistent hypoglycemia.

Glucagon- test (C- peptide)

There is a glucagon, which is, however, used in everyday medical practice rarely. It is used to test the stimulation of β - cells of the pancreas ( gain) for the differentiation of diabetes type I and type II

Implementation

Assessment

  • An increase of C-peptide at least 0.5 nmol / l and / or more than 1.0 nmol / L indicates functional β - cells.
  • Blood glucose should be always determined to detect the degree of the pre-stimulation of the β - cells.
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