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.
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 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.
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 6.
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.
- 1. Pearson MJ, Unger RH, Holland WL. Clinical Trials, Triumphs, and Tribulations of Glucagon Receptor Antagonists. (2016) Diabetes care. 39 (7): 1075-7. doi:10.2337/dci15-0033 - Pubmed
- 2. Jiang G, Zhang BB. Glucagon and regulation of glucose metabolism. (2003) American journal of physiology. Endocrinology and metabolism. 284 (4): E671-8. doi:10.1152/ajpendo.00492.2002 - Pubmed
- 3. Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA. Pancreatic Extracts in the Treatment of Diabetes Mellitus. (1922) Canadian Medical Association journal. 12 (3): 141-6. Pubmed
- 4. Yee J, Hung RK, Akerkar GA, Wall SD. The usefulness of glucagon hydrochloride for colonic distention in CT colonography. (1999) AJR. American journal of roentgenology. 173 (1): 169-72. doi:10.2214/ajr.173.1.10397121 - Pubmed
- 5. Rogalla P, Lembcke A, Rückert JC, Hein E, Bollow M, Rogalla NE, Hamm B. Spasmolysis at CT colonography: butyl scopolamine versus glucagon. (2005) Radiology. 236 (1): 184-8. doi:10.1148/radiol.2353040007 - Pubmed
- 6. de Haan MC, Boellaard TN, Bossuyt PM, Stoker J. Colon distension, perceived burden and side-effects of CT-colonography for screening using hyoscine butylbromide or glucagon hydrochloride as bowel relaxant. (2012) European journal of radiology. 81 (8): e910-6. doi:10.1016/j.ejrad.2012.05.020 - Pubmed