Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.
Indiana Biosciences Research Institute, Indianapolis, IN, USA.
FEBS J. 2021 Apr;288(8):2622-2644. doi: 10.1111/febs.15800. Epub 2021 Mar 22.
The incidence of obesity and type 2 diabetes (T2D) has been increasing steadily worldwide. It is estimated that by 2045 more than 800 million people will be suffering from diabetes. Despite the advancements in modern medicine, more effective therapies for treating obesity and T2D are needed. G protein-coupled receptors (GPCRs) have emerged as important drug targets for various chronic diseases, including obesity, T2D, and liver diseases. During the past two decades, many laboratories worldwide focused on understanding the role of GPCR signaling in regulating glucose metabolism and energy homeostasis. The information gained from these studies can guide the development of novel therapeutic agents. In this review, we summarize recent studies providing insights into the role of GPCR signaling in peripheral, metabolically important tissues such as pancreas, liver, skeletal muscle, and adipose tissue, focusing primarily on the use of mutant animal models and human data.
肥胖和 2 型糖尿病（T2D）的发病率在全球范围内持续稳步上升。据估计，到 2045 年，将有超过 8 亿人患有糖尿病。尽管现代医学取得了进步，但仍需要更有效的治疗肥胖和 T2D 的疗法。G 蛋白偶联受体（GPCR）已成为治疗肥胖、T2D 和肝脏疾病等多种慢性疾病的重要药物靶点。在过去的二十年中，全球许多实验室都专注于了解 GPCR 信号在调节葡萄糖代谢和能量平衡中的作用。这些研究获得的信息可以指导新型治疗药物的开发。在这篇综述中，我们总结了最近的研究，这些研究深入了解了 GPCR 信号在胰腺、肝脏、骨骼肌和脂肪组织等外周代谢重要组织中的作用，主要侧重于使用突变动物模型和人类数据。
