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SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes
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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-GqPKC-dependent mechanism in human beta cells. Mice with beta 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.
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SABADELL BASALLOTE, Joan, et al. SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes. Journal of Clinical Investigation. 2024. Vol. 134, num. 12. ISSN 1558-8238. [consulted: 6 of June of 2026]. Available at: https://hdl.handle.net/2445/214943