Department of Endocrinology, The Second Hospital of He Bei Medical University, Shijiazhuang, China.
Diabetes Metab Res Rev. 2011 May;27(4):318-30. doi: 10.1002/dmrr.1182.
This review addresses the roles of Rho/Rho-kinase (ROCK) pathway in the pathogenesis of diabetes complications. Diabetes can cause many serious complications and can result in physical disability or even increased mortality. However, there are not many effective ways to treat these complications. The small guanosine-5'-triphosphate-binding protein Rho and its downstream target Rho-kinase mediate important cellular functions, such as cell morphology, motility, secretion, proliferation, and gene expression. Recently, the Rho/Rho-kinase pathway has attracted a great deal of attention in diabetes-related research. These studies have provided evidence that the activity and gene expression of Rho-kinase are upregulated in some tissues in animal models of type 1 or type 2 diabetes and in cell lines cultured with high concentrations of glucose. Inhibitors of Rho-kinase could prevent or ameliorate the pathological changes in diabetic complications. The inhibitory effects of statins on the Rho/Rho-kinase signalling pathway may also play a role in the prevention of diabetic complications. However, the precise molecular mechanism by which the Rho/Roh-kinase pathway participates in the development or progression of diabetic complications has not been extensively investigated. This article evaluates the relationship between Rho/Roh-kinase activation and diabetic complications, as well as the roles of Roh-kinase inhibitors and statins in the complications of diabetes, with the objective of providing a novel target for the treatment of long-term diabetic complications.
这篇综述探讨了 Rho/Rho-kinase(ROCK)通路在糖尿病并发症发病机制中的作用。糖尿病可引起许多严重并发症,并导致身体残疾甚至死亡率增加。然而,目前治疗这些并发症的有效方法并不多。小分子鸟苷三磷酸结合蛋白 Rho 及其下游靶标 Rho-kinase 介导重要的细胞功能,如细胞形态、运动性、分泌、增殖和基因表达。最近,Rho/Rho-kinase 通路在与糖尿病相关的研究中引起了广泛关注。这些研究提供了证据表明,1 型或 2 型糖尿病动物模型中某些组织以及高浓度葡萄糖培养的细胞系中 Rho-kinase 的活性和基因表达上调。Rho-kinase 的抑制剂可预防或改善糖尿病并发症的病理变化。他汀类药物对 Rho/Rho-kinase 信号通路的抑制作用可能也在预防糖尿病并发症中发挥作用。然而,Rho/Roh-kinase 通路参与糖尿病并发症的发展或进展的确切分子机制尚未得到广泛研究。本文评估了 Rho/Roh-kinase 激活与糖尿病并发症之间的关系,以及 Rho-kinase 抑制剂和他汀类药物在糖尿病并发症中的作用,以期为长期糖尿病并发症的治疗提供新的靶点。