G protein-linked cell signaling and cardiovascular functions in diabetes/hyperglycemia.
Vascular complications, including impaired contractility and increased cell proliferation, are the most common complications with diabetes. Chronic hyperglycemia seems to be an important contributing factor in this process. Various signaling pathways are implicated in diabetes/hyperglycemia-induced impaired vascular functions. Nonenzymatic glycation, enhanced production of diacylglycerol, increased activity of membranous protein kinase C (PKC), and increased oxidative stress have been proposed to explain the adverse effects of hyperglycemia on vascular smooth muscle cells. Hyperglycemia-induced stimulation of L-type Ca2+ channel via G protein-coupled adenylyl cyclase/cAMP and phospholipase C/PKC pathways also has been shown. In addition, hyperglycemia has been reported to decrease the availability of nitric oxide in humans, which may contribute to all the hemodynamic and physiological changes occurring in diabetes. G protein-adenylyl cyclase signaling that plays an important role in the regulation of cardiovascular functions also has been reported to be impaired in diabetes and under hyperglycemic conditions. In this review article, various G protein-linked cell signaling and functions in diabetes and hyperglycemia are discussed.
Hashim
Shehla
S
Department of Physiology and Groupe de recherche sur le système nerveux autonome (GRSNA), Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
Li
Yuan
Y
Anand-Srivastava
Madhu B
MB
D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D002320:Cardiovascular Physiological Phenomena; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000378:metabolism; D048909:Diabetes Complications / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D008955:Models, Cardiovascular; D009569:Nitric Oxide / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology*
D009569:Nitric Oxide; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases