Glucagon lowers glycemia when β-cells are active.

Journal Article (Journal Article)

Glucagon and insulin are commonly believed to have counteracting effects on blood glucose levels. However, recent studies have demonstrated that glucagon has a physiologic role to activate β-cells and enhance insulin secretion. To date, the actions of glucagon have been studied mostly in fasting or hypoglycemic states, yet it is clear that mixed-nutrient meals elicit secretion of both glucagon and insulin, suggesting that glucagon also contributes to glucose regulation in the postprandial state. We hypothesized that the elevated glycemia seen in the fed state would allow glucagon to stimulate insulin secretion and reduce blood glucose. In fact, exogenous glucagon given under fed conditions did robustly stimulate insulin secretion and lower glycemia. Exogenous glucagon given to fed Gcgr:Glp1rβcell-/- mice failed to stimulate insulin secretion or reduce glycemia, demonstrating the importance of an insulinotropic glucagon effect. The action of endogenous glucagon to reduce glycemia in the fed state was tested with administration of alanine, a potent glucagon secretagogue. Alanine raised blood glucose in fasted WT mice or fed Gcgr:Glp1rβcell-/- mice, conditions where glucagon is unable to stimulate β-cell activity. However, alanine given to fed WT mice produced a decrease in glycemia, along with elevated insulin and glucagon levels. Overall, our data support a model in which glucagon serves as an insulinotropic hormone in the fed state and complements rather than opposes insulin action to maintain euglycemia.

Full Text

Duke Authors

Cited Authors

  • Capozzi, ME; Wait, JB; Koech, J; Gordon, AN; Coch, RW; Svendsen, B; Finan, B; D'Alessio, DA; Campbell, JE

Published Date

  • July 23, 2019

Published In

Volume / Issue

  • 5 / 16

PubMed ID

  • 31335319

Pubmed Central ID

  • PMC6777806

Electronic International Standard Serial Number (EISSN)

  • 2379-3708

Digital Object Identifier (DOI)

  • 10.1172/jci.insight.129954


  • eng

Conference Location

  • United States