1. SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes.
- Author
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Sabadell-Basallote, Joan, Astiarraga, Brenno, Castaño, Carlos, Ejarque, Miriam, Repollés-de-Dalmau, Maria, Quesada, Ivan, Blanco, Jordi, Núñez-Roa, Catalina, Rodríguez-Peña, M-Mar, Martínez, Laia, De Jesus, Dario F., Marroquí, Laura, Bosch, Ramon, Montanya, Eduard, Sureda, Francesc X., Tura, Andrea, Mari, Andrea, Kulkarni, Rohit N., Vendrell, Joan, and Fernández-Veledo, Sonia
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INSULIN , *SECRETION , *PREDIABETIC state , *TYPE 2 diabetes , *GLUCOSE - Abstract
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-GqPKC–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. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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