Rayasam Geetha Vani, Tulasi Vamshi Krishna, Davis Joseph Alex, Bansal Vinay S
Metabolic Disorders, Department of Pharmacology, Research & Development (R&D III), Ranbaxy, Sector 18, Gurgaon, Haryana, India.
Expert Opin Ther Targets. 2007 May;11(5):661-71. doi: 10.1517/14728222.11.5.661.
G-protein-coupled receptors (GPCRs) are key regulators of several physiological functions. Their roles in cellular signal transduction have made them the target for majority of all currently prescribed drugs. Additionally, there are many orphan GPCRs that provide potential novel therapeutic targets. Several GPCRs are involved in metabolic regulation and glucose homeostasis such as GLP-1 receptor, glucagon receptor, adiponectin receptor and so on. Recently, free fatty acids (FFAs) have been demonstrated as ligands for orphan GPCRs and have been proposed to play a critical role in physiological glucose homeostasis. GPR40 and GPR120 are activated by medium and long-chain FFAs, whereas GPR41 and GPR43 can be activated by short-chain FFAs. GPR40, which is preferentially expressed in pancreatic beta-cells, mediates the majority of the effects of FFAs on insulin secretion. In this review, these findings and also critical analysis of these GPCRs as novel targets for diabetes are discussed.
G蛋白偶联受体（GPCRs）是多种生理功能的关键调节因子。它们在细胞信号转导中的作用使其成为目前所有处方药的主要靶点。此外，还有许多孤儿GPCRs，它们是潜在的新型治疗靶点。几种GPCRs参与代谢调节和葡萄糖稳态，如胰高血糖素样肽-1受体、胰高血糖素受体、脂联素受体等。最近，游离脂肪酸（FFAs）已被证明是孤儿GPCRs的配体，并被认为在生理性葡萄糖稳态中起关键作用。GPR40和GPR120被中链和长链FFAs激活，而GPR41和GPR43可被短链FFAs激活。GPR40优先表达于胰腺β细胞，介导FFAs对胰岛素分泌的大部分作用。在这篇综述中，将讨论这些发现以及对这些作为糖尿病新靶点的GPCRs的批判性分析。
