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SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes
- Source :
- Journal of Clinical Investigation. June 15, 2024, Vol. 134 Issue 12
- Publication Year :
- 2024
-
Abstract
- Pancreatic [beta] 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 [beta] 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-Gq-PKC-dependent mechanism in human [beta] cells. Mice with [beta] cell-specific Sucnrl 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.<br />Introduction Insulin secretion by pancreatic [beta] cells is crucial for blood glucose homeostasis and is tightly controlled by a complex network of hormones, nutrients, and neurotransmitters. Impaired [beta] cell function [...]
- Subjects :
- Metabolic regulation -- Research
Diabetes -- Research
Pancreatic beta cells -- Health aspects -- Physiological aspects
Insulin -- Health aspects -- Physiological aspects
Prediabetic state -- Development and progression
Glucose metabolism -- Research
Cell receptors -- Health aspects -- Physiological aspects
Health care industry
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 134
- Issue :
- 12
- Database :
- Gale General OneFile
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.801951049
- Full Text :
- https://doi.org/10.1172/JCI173214