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Glucagon lowers glycemia when β-cells are active.

Publication ,  Journal Article
Capozzi, ME; Wait, JB; Koech, J; Gordon, AN; Coch, RW; Svendsen, B; Finan, B; D'Alessio, DA; Campbell, JE
Published in: JCI Insight
July 23, 2019

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.

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Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

July 23, 2019

Volume

5

Issue

16

Location

United States

Related Subject Headings

  • Postprandial Period
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Islets of Langerhans
  • Insulin-Secreting Cells
  • Insulin Secretion
  • Insulin
  • Hypoglycemia
 

Citation

APA
Chicago
ICMJE
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Capozzi, M. E., Wait, J. B., Koech, J., Gordon, A. N., Coch, R. W., Svendsen, B., … Campbell, J. E. (2019). Glucagon lowers glycemia when β-cells are active. JCI Insight, 5(16). https://doi.org/10.1172/jci.insight.129954
Capozzi, Megan E., Jacob B. Wait, Jepchumba Koech, Andrew N. Gordon, Reilly W. Coch, Berit Svendsen, Brian Finan, David A. D’Alessio, and Jonathan E. Campbell. “Glucagon lowers glycemia when β-cells are active.JCI Insight 5, no. 16 (July 23, 2019). https://doi.org/10.1172/jci.insight.129954.
Capozzi ME, Wait JB, Koech J, Gordon AN, Coch RW, Svendsen B, et al. Glucagon lowers glycemia when β-cells are active. JCI Insight. 2019 Jul 23;5(16).
Capozzi, Megan E., et al. “Glucagon lowers glycemia when β-cells are active.JCI Insight, vol. 5, no. 16, July 2019. Pubmed, doi:10.1172/jci.insight.129954.
Capozzi ME, Wait JB, Koech J, Gordon AN, Coch RW, Svendsen B, Finan B, D’Alessio DA, Campbell JE. Glucagon lowers glycemia when β-cells are active. JCI Insight. 2019 Jul 23;5(16).

Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

July 23, 2019

Volume

5

Issue

16

Location

United States

Related Subject Headings

  • Postprandial Period
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Islets of Langerhans
  • Insulin-Secreting Cells
  • Insulin Secretion
  • Insulin
  • Hypoglycemia