Shandong Collaborative Innovation Center for Diagnosis, Treatment and Behavioral Interventions of Mental Disorders, Institute of Mental Health, Jining Medical University, Jianshe South Road No.45, Rencheng District, Jining 272013, China.
Shandong Key Laboratory of Behavioral Medicine, School of Mental Health, Jining Medical University, Jianshe South Road No.45, Rencheng District, Jining 272013, China.
Cells. 2022 Dec 2;11(23):3897. doi: 10.3390/cells11233897.
Type 2 diabetes mellitus (T2DM) is a complex and heterogeneous disease that primarily results from impaired insulin secretion or insulin resistance (IR). G protein-coupled receptors (GPCRs) are proposed as therapeutic targets for T2DM. GPCRs transduce signals via the Gα protein, playing an integral role in insulin secretion and IR. The regulators of G protein signaling (RGS) family proteins can bind to Gα proteins and function as GTPase-activating proteins (GAP) to accelerate GTP hydrolysis, thereby terminating Gα protein signaling. Thus, RGS proteins determine the size and duration of cellular responses to GPCR stimulation. RGSs are becoming popular targeting sites for modulating the signaling of GPCRs and related diseases. The R4 subfamily is the largest RGS family. This review will summarize the research progress on the mechanisms of R4 RGS subfamily proteins in insulin secretion and insulin resistance and analyze their potential value in the treatment of T2DM.
2 型糖尿病（T2DM）是一种复杂的异质性疾病，主要由胰岛素分泌受损或胰岛素抵抗（IR）引起。G 蛋白偶联受体（GPCR）被认为是 T2DM 的治疗靶点。GPCR 通过 Gα 蛋白传递信号，在胰岛素分泌和 IR 中发挥重要作用。G 蛋白信号转导调节因子（RGS）家族蛋白可与 Gα 蛋白结合，并作为 GTP 酶激活蛋白（GAP）发挥作用，加速 GTP 水解，从而终止 Gα 蛋白信号转导。因此，RGS 蛋白决定了细胞对 GPCR 刺激的反应幅度和持续时间。RGS 蛋白正成为调节 GPCR 及其相关疾病信号转导的热门靶点。R4 亚家族是最大的 RGS 家族。本文将总结 R4 RGS 亚家族蛋白在胰岛素分泌和胰岛素抵抗中的作用机制的研究进展，并分析其在治疗 T2DM 中的潜在价值。
