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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/214943
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, ASTIARRAGA, Brenno, CASTAÑO, Carlos, EJARQUE, Miriam, REPOLLÉS DE DALMAU, Maria, QUESADA, Iván, BLANCO, Jordi, NÚÑEZ ROA, Catalina, RODRÍGUEZ PEÑA, M. mar, MARTÍNEZ, Laia, JESUS, Dario f. de, MARROQUÍ, Laura, BOSCH, Ramon, MONTANYA, Eduard, SUREDA, Francesc x., TURA, Andrea, MARI, Andrea, KULKARNI, Rohit n., VENDRELL, Joan, FERNÁNDEZ VELEDO, Sonia. SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes. _Journal of Clinical Investigation_. 2024. Vol. 134, núm. 12. [consulta: 10 de gener de 2026]. ISSN: 1558-8238. [Disponible a: https://hdl.handle.net/2445/214943]