التفاصيل البيبلوغرافية
| العنوان: |
SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes. |
| المؤلفون: |
Sabadell-Basallote, Joan1,2,3,4, Astiarraga, Brenno1,2, Castaño, Carlos1,2, Ejarque, Miriam1,2, Repollés-de-Dalmau, Maria1,2,3, Quesada, Ivan2,5, Blanco, Jordi3, Núñez-Roa, Catalina1,2, Rodríguez-Peña, M-Mar1,2, Martínez, Laia1, De Jesus, Dario F.4, Marroquí, Laura2,5, Bosch, Ramon1,3,6, Montanya, Eduard2,7, Sureda, Francesc X.3, Tura, Andrea8, Mari, Andrea8, Kulkarni, Rohit N.4, Vendrell, Joan1,2,3, Fernández-Veledo, Sonia1,2,3 |
| المصدر: |
Journal of Clinical Investigation. 6/17/2024, Vol. 134 Issue 12, p1-15. 15p. |
| مصطلحات موضوعية: |
*INSULIN, *SECRETION, *PREDIABETIC state, *TYPE 2 diabetes, *GLUCOSE |
| مستخلص: |
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] |
| قاعدة البيانات: |
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