8.Diabetes/Hyperglycemia differentially Regulate Giα and Gqα Protein Expression and Associated Signalling in Vascular Smooth Muscle Cells

摘要

The impaired vascular contractility and increased cell proliferation are the most common vascular complications associated with diabetes and the chronic hyperglycemia appears to be an important contributing factor in this process. Various signalling pathways are implicated in diabetes/hyperglycemia-induced impaired vascular functions. Increased oxidative stress, non-enzymatic glycation, enhanced production of diacylglycerol, increased activity of protein kinase C, MAP Kinases and other signalling pathways have been proposed to explain the adverse effects of hyperglycemia on vascular smooth muscle cells (VSMC). Hyperglycemia-induced stimulation of L-type Ca~(2+) channel via G-protein-coupled adenylyl cyclase/cAMP and phospholipase C/PKC pathways has also been shown. In addition, hyperglycemia has been reported to decrease the availability of nitric oxide and increase the formation of peroxynitrite which may contribute to all the hemodynamic and physiological changes occurring in diabetes. Furthermore, G-protein-adenylyl cyclase signaling and phosphatidyl inositol (PI) turnover that play an important role in the regulation of cardiovascular functions has also been reported to be impaired in diabetes and under hyperglycemic conditions. In this review, we have highlighted some key signalling pathways, such as G-protein/adenylyl cyclase and Gq protein/PI turnover, and have discussed their differential regulation in diabetes and in response to hyperglycemia as well as their contributions in the development of vascular complications.