(08-05-16) Evidence of Extrapancreatic Glucagon Secretion in Man

Lund A1, Bagger JI1, Wewer Albrechtsen NJ2, Christensen M1, Grøndahl M3, Hartmann B4, Mathiesen ER5, Hansen CP6, Storkholm JH6, van Hall G7, Rehfeld JF8, Hornburg D9, Meissner F9, Mann M10, Larsen S3, Holst JJ4, Vilsbøll T3, Knop FK11.


Abstract
Glucagon is believed to be a pancreas-specific hormone, and hyperglucagonemia has been shown to contribute significantly to the hyperglycemic state of patients with diabetes. This hyperglucagonemia has been thought to arise from α-cell insensitivity to suppressive effects of glucose and insulin combined with reduced insulin secretion. We hypothesized that postabsorptive hyperglucagonemia represents a gut-dependent phenomenon and subjected 10 totally pancreatectomized patients and 10 healthy control subjects to a 75-g oral glucose tolerance test and a corresponding isoglycemic intravenous glucose infusion. We applied novel analytical methods of plasma glucagon (sandwich ELISA and mass spectrometry-based proteomics) and show that 29-amino acid glucagon circulates in patients without a pancreas and that glucose stimulation of the gastrointestinal tract elicits significant hyperglucagonemia in these patients. These findings emphasize the existence of extrapancreatic glucagon (perhaps originating from the gut) in man and suggest that it may play a role in diabetes secondary to total pancreatectomy.

Fonte: Diabetes. 2016 Mar;65(3):585-97. doi: 10.2337/db15-1541. Epub 2015 Dec 15.

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