The Limited Role of Glucagon for Ketogenesis During Fasting or in Response to SGLT2 Inhibition.
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.
Duke Scholars
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- Sodium-Glucose Transporter 2 Inhibitors
- Sodium-Glucose Transporter 2
- Mice
- Lipolysis
- Insulin
- Glucosides
- Glucagon
- Gene Expression Regulation
- Food Deprivation
- Epinephrine
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Sodium-Glucose Transporter 2 Inhibitors
- Sodium-Glucose Transporter 2
- Mice
- Lipolysis
- Insulin
- Glucosides
- Glucagon
- Gene Expression Regulation
- Food Deprivation
- Epinephrine