Priyadarshini Medha, Wicksteed Barton, Schiltz Gary E, Gilchrist Annette, Layden Brian T
Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, IL 60208, USA; Department of Pharmacology, Northwestern University, Chicago, IL 60611, USA.
Trends Endocrinol Metab. 2016 Sep;27(9):653-664. doi: 10.1016/j.tem.2016.03.011. Epub 2016 Apr 15.
Nutrient sensing receptors are key metabolic mediators of responses to dietary and endogenously derived nutrients. These receptors are largely G-protein-coupled receptors (GPCRs) and many are gaining significant interest as drug targets with a potential therapeutic role in metabolic diseases. A distinct subclass of nutrient sensing GPCRs, two short chain fatty acid (SCFA) receptors (FFA2 and FFA3) are uniquely responsive to gut microbiota derived nutrients (such as acetate, propionate, and butyrate). Pharmacological, molecular, and genetic studies have investigated their role in organismal glucose metabolism and recently in pancreatic β cell biology. Here, we summarize the present knowledge on the role of these receptors as metabolic sensors in β cell function and physiology, revealing new therapeutic opportunities for type 2 diabetes.
营养感应受体是对膳食和内源性营养物质作出反应的关键代谢介质。这些受体主要是G蛋白偶联受体(GPCRs),其中许多作为药物靶点正引起人们极大的兴趣,在代谢性疾病中具有潜在的治疗作用。营养感应GPCRs的一个独特亚类,即两种短链脂肪酸(SCFA)受体(FFA2和FFA3),对肠道微生物群衍生的营养物质(如乙酸盐、丙酸盐和丁酸盐)具有独特的反应性。药理学、分子和遗传学研究已经探讨了它们在机体葡萄糖代谢以及最近在胰腺β细胞生物学中的作用。在这里,我们总结了关于这些受体作为β细胞功能和生理学代谢传感器作用的现有知识,揭示了2型糖尿病新的治疗机会。