SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes

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 hor...

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Detalles Bibliográficos
Autores: Sabadell-Basallote, Joan, Astiarraga, Brenno, Castaño, Carlos, Ejarque, Miriam, Repollés de Dalmau, Maria, Quesada, Ivan, Blanco, Jordi, Núñez-Roa, Catalina, Rodríguez-Peña, M., Martínez, Laia, F De Jesus, Dario, Marroqui Esclapez, Laura, Bosch, Ramon, Montanya, Eduard, Sureda, Francesc, Tura, Andrea, Mari, Andrea, Kulkarni, Rohit N., Vendrell, Joan, Fernández-Veledo, Sonia
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Miguel Hernández de Elche
Repositorio:REDIUMH. Depósito Digital de la UMH
OAI Identifier:oai:dspace.umh.es:11000/38552
Acceso en línea:https://hdl.handle.net/11000/38552
Access Level:acceso abierto
Palabra clave:CDU::6 - Ciencias aplicadas::61 - Medicina::612 - Fisiología
Descripción
Sumario: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-Gq-PKC–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.