Revision 15 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, although its clinical efficacy is controversial. 

Structure

Glucagon is a 29-amino acid polypeptide hormone that is enzymatically-derived from proglucagon, its biochemical precursor. It is synthesized in and secreted by α-cells in the islets of Langerhans of the pancreas. Recent evidence suggests that it is also secreted by the gut itself.

Glucose regulation

Glucose homeostasis is very complex.  The main action of glucagon is hyperglycemic, achieved through hepatic 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, γ-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. 

Use in imaging

Glucagon is used by some radiologists as an antiperistaltic agent to promote bowel distension in GI examinations, e.g. CT colonography, gastric emptying studies. 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 (Buscopan®) and glucagon found that hyoscine was a more effective agent 5.  A more recent head-to-head study found that patients reported less discomfort with hyoscine, and again bowel distension was better, than with glucagon.

In addition, glucagon has a higher unit cost than hyoscine, more onerous storage requirements, is less straightforward to administer and has a shorter biological half-life. 

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, which they named glucagon, was responsible 3. It was only in 1955 that the polypeptide responsible was finally purified 1.

Practical points

  • IV glucagon should be administered slowly over 40-60 seconds
    • rapid injection may cause cramps or vomiting
  • glucagon is contraindicated in patients with an insulinomapheochromocytoma, or glucagonoma

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