Revision 8 for 'Glucagon'

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Glucagon

Glucagon is a polypeptide hormone central to the regulation of glucose homeostasis, acting as an antagonist to insulin. In imaging it is used as an antiperistaltic agent in GI studies.

Structure and mechanism of action

Glucagon is a 29-amino acid polypeptide hormone that is enzymatically-derived from proglucagon, its biochemical precursor. Glucagon acts via a G protein-coupled seven-domain-transmembrane receptor.

Glucose regulation

Glucose homeostasis is very complex.  The main action of glucagon is hyperglycemic, achieved through gluconeogenesis and glycogenolysis. Glucagon is secreted from α-cells of the pancreas when blood sugar levels decrease.  Fundamentally it ensures that the supply of glucose to the brain is maintained 1.

Insulin, gamma-aminobutyric acid (GABA) and leptin are the main actors in inhibiting glucagon secretion. 

Pathology

Hyperglucagonemia has been found in all cases of diabetes mellitus, therefore glucagon has become a major target for the pharmaceutical industry in the development of new diabetic medications 1.

In the rare tumor glucagonoma, the hypersecretion of glucagon leads to its clinical presentation. 

Pharmaceutical

Glucagon is used by some radiologists as an antiperistaltic agent to promote bowel distension in GI examinations, e.g. CT colonography. However evidence for its efficacy for this is lacking. A widely-cited study published in 1999 did not find any improvement in colonic distension with preprocedural administration of glucagon 4.

A 2005 head to head study comparing hyoscine butylbromide and glucagon found that hyoscine was a more effective agent 

gastric emptying studies. 

History and etymology

Unusually glucagon was named before it was discovered! 
In 1922 Banting et al. found that crude pancreatic extracts given to children with diabetes produced a short-lived elevation of the serum glucose before insulin's desired hypoglycemic effect. It was postulated that an unknown substance, named glucagon, was responsible 3. It was only in 1955 that the polypeptide responsible was finally purified 1.

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