Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Illinois at Chicago, Chicago, Illinois.
Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois.
Endocrinology. 2018 Jun 1;159(6):2495-2505. doi: 10.1210/en.2018-00296.
The G protein-coupled receptors, free fatty acid (FFA) receptors 2 and 3 (FFA2 and FFA3), belonging to the free fatty acid receptor (FFAR) class, sense a distinct class of nutrients, short chain fatty acids (SCFAs). These receptors participate in both immune and metabolic regulation. The latter includes a role in regulating secretion of metabolic hormones. It was only recently that their role in pancreatic β cells was recognized; these receptors are known now to affect not only insulin secretion but also β-cell survival and proliferation. These observations make them excellent potential therapeutic targets in type 2 diabetes. Moreover, expression on both immune and β cells makes these receptors possible targets in type 1 diabetes. Furthermore, SCFAs are generated by gut microbial fermentative activity; therefore, signaling by FFA2 and FFA3 represents an exciting novel link between the gut microbiota and the β cells. This review enumerates the role of these receptors in β cells revealed so far and discusses possible roles in clinical translation.
G 蛋白偶联受体，游离脂肪酸（FFA）受体 2 和 3（FFA2 和 FFA3），属于游离脂肪酸受体（FFAR）类，感知一类独特的营养素，即短链脂肪酸（SCFAs）。这些受体参与免疫和代谢调节。后者包括调节代谢激素分泌的作用。直到最近才认识到它们在胰腺β细胞中的作用；现在已知这些受体不仅影响胰岛素分泌，还影响β细胞的存活和增殖。这些观察结果使它们成为 2 型糖尿病的理想潜在治疗靶点。此外，在免疫细胞和β细胞上的表达使这些受体成为 1 型糖尿病的潜在靶点。此外，SCFAs 是由肠道微生物发酵活动产生的；因此，FFA2 和 FFA3 的信号转导代表了肠道微生物群和β细胞之间令人兴奋的新联系。这篇综述列举了迄今为止这些受体在β细胞中所揭示的作用，并讨论了在临床转化中的可能作用。
