The Limited Role of Glucagon for Ketogenesis During Fasting or in Response to SGLT2 Inhibition.
Animals
Benzhydryl Compounds
/ pharmacology
Blood Glucose
Epinephrine
/ pharmacology
Food Deprivation
Gene Expression Regulation
/ drug effects
Glucagon
/ metabolism
Glucosides
/ pharmacology
Insulin
/ blood
Lipolysis
/ drug effects
Mice
Sodium-Glucose Transporter 2
/ genetics
Sodium-Glucose Transporter 2 Inhibitors
/ pharmacology
Journal
Diabetes
ISSN: 1939-327X
Titre abrégé: Diabetes
Pays: United States
ID NLM: 0372763
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
09
12
2019
accepted:
27
01
2020
pubmed:
2
2
2020
medline:
28
10
2020
entrez:
2
2
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32005706
pii: db19-1216
doi: 10.2337/db19-1216
pmc: PMC7171961
doi:
Substances chimiques
Benzhydryl Compounds
0
Blood Glucose
0
Glucosides
0
Insulin
0
Slc5a2 protein, mouse
0
Sodium-Glucose Transporter 2
0
Sodium-Glucose Transporter 2 Inhibitors
0
dapagliflozin
1ULL0QJ8UC
Glucagon
9007-92-5
Epinephrine
YKH834O4BH
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
882-892Subventions
Organisme : NIDDK NIH HHS
ID : F32 DK116542
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK101991
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK123075
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007012
Pays : United States
Informations de copyright
© 2020 by the American Diabetes Association.
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