Sabadell Basallote, JoanAstiarraga, BrennoCastaño, CarlosEjarque, MiriamRepollés de Dalmau, MariaQuesada, IvánBlanco, JordiNúñez Roa, CatalinaRodríguez Peña, M. MarMartínez, LaiaJesus, Dario F. deMarroquí, LauraBosch, RamonMontanya, EduardSureda, Francesc X.Tura, AndreaMari, AndreaKulkarni, Rohit N.Vendrell, JoanFernández Veledo, Sonia2024-09-032024-09-032024-05-071558-8238https://hdl.handle.net/2445/214943Pancreatic 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.15 p.application/pdfengcc by (c) Sabadell Basallote, Joan et al, 2024http://creativecommons.org/licenses/by/3.0/es/DiabetisMetabòlitsDiabetesMetabolitesinfo:eu-repo/semantics/article2024-07-11info:eu-repo/semantics/openAccess38713514