Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.
Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.
Trends Endocrinol Metab. 2021 Feb;32(2):118-129. doi: 10.1016/j.tem.2020.11.008. Epub 2020 Dec 23.
β-Arrestin-1 and -2 are intracellular proteins that are able to inhibit signaling via G protein-coupled receptors (GPCRs). However, both proteins can also modulate cellular functions in a G protein-independent fashion. During the past few years, studies with mutant mice selectivity lacking β-arrestin-1 and/or -2 in metabolically important cell types have led to novel insights into the mechanisms through which β-arrestins regulate key metabolic processes in vivo, including whole-body glucose and energy homeostasis. The novel information gained from these studies should inform the development of novel drugs, including β-arrestin- or G protein-biased GPCR ligands, that could prove useful for the therapy of several important pathophysiological conditions, including type 2 diabetes and obesity.
β-arrestin-1 和 -2 是能够抑制 G 蛋白偶联受体 (GPCR) 信号转导的细胞内蛋白。然而，这两种蛋白也可以以非 G 蛋白依赖的方式调节细胞功能。在过去的几年中，使用选择性缺乏代谢重要细胞类型中的β-arrestin-1 和/或 -2 的突变小鼠进行的研究，为β-arrestin 调节体内关键代谢过程的机制提供了新的见解，包括全身葡萄糖和能量稳态。从这些研究中获得的新信息应该为新型药物的开发提供信息，包括β-arrestin 或 G 蛋白偏向性 GPCR 配体，这可能对治疗几种重要的病理生理状况（包括 2 型糖尿病和肥胖症）有用。
