The Limited Role of Glucagon for Ketogenesis During Fasting or in Response to SGLT2 Inhibition.

Journal Article (Journal Article)

Glucagon is classically described as a counterregulatory hormone that plays an essential role in the protection against hypoglycemia. In addition to its role in the regulation of glucose metabolism, glucagon has been described to promote ketosis in the fasted state. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a new class of glucose-lowering drugs that act primarily in the kidney, but some reports have described direct effects of SGLT2i on α-cells to stimulate glucagon secretion. Interestingly, SGLT2 inhibition also results in increased endogenous glucose production and ketone production, features common to glucagon action. Here, we directly test the ketogenic role of glucagon in mice, demonstrating that neither fasting- nor SGLT2i-induced ketosis is altered by interruption of glucagon signaling. Moreover, any effect of glucagon to stimulate ketogenesis is severely limited by its insulinotropic actions. Collectively, our data suggest that fasting-associated ketosis and the ketogenic effects of SGLT2 inhibitors occur almost entirely independent of glucagon.

Full Text

Duke Authors

Cited Authors

  • Capozzi, ME; Coch, RW; Koech, J; Astapova, II; Wait, JB; Encisco, SE; Douros, JD; El, K; Finan, B; Sloop, KW; Herman, MA; D'Alessio, DA; Campbell, JE

Published Date

  • May 2020

Published In

Volume / Issue

  • 69 / 5

Start / End Page

  • 882 - 892

PubMed ID

  • 32005706

Pubmed Central ID

  • PMC7171961

Electronic International Standard Serial Number (EISSN)

  • 1939-327X

Digital Object Identifier (DOI)

  • 10.2337/db19-1216


  • eng

Conference Location

  • United States