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SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes.
- Source :
-
Journal of Clinical Investigation . 6/17/2024, Vol. 134 Issue 12, p1-15. 15p. - Publication Year :
- 2024
-
Abstract
- Pancreatic β cell dysfunction is a key feature of type 2 diabetes, and novel regulators of insulin secretion are desirable. Here, we report that succinate receptor 1 (SUCNR1) is expressed in β cells and is upregulated in hyperglycemic states in mice and humans. We found that succinate acted as a hormone-like metabolite and stimulated insulin secretion via a SUCNR1-GqPKC–dependent mechanism in human β cells. Mice with β cell–specific Sucnr1 deficiency exhibited impaired glucose tolerance and insulin secretion on a high-fat diet, indicating that SUCNR1 is essential for preserving insulin secretion in diet-induced insulin resistance. Patients with impaired glucose tolerance showed an enhanced nutrition-related succinate response, which correlates with the potentiation of insulin secretion during intravenous glucose administration. These data demonstrate that the succinate/SUCNR1 axis is activated by high glucose and identify a GPCR-mediated amplifying pathway for insulin secretion relevant to the hyperinsulinemia of prediabetic states. [ABSTRACT FROM AUTHOR]
- Subjects :
- *INSULIN
*SECRETION
*PREDIABETIC state
*TYPE 2 diabetes
*GLUCOSE
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 134
- Issue :
- 12
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- 177976619
- Full Text :
- https://doi.org/10.1172/JCI173214