Diabetic cardiomyopathy: the significance of creatine.
Diabetics exhibit a greater incidence of cardiovascular disease than non-diabetics. The vascular changes that occur are well documented and are thought to promote other clinical manifestations such as cardiomyopathy. Research has shown that the pathogenic events in the myocyte may occur independently of atherosclerotic processes. The atherosclerotic changes in diabetes involve non-enzymatic glycation of extracellular basement membrane proteins. We hypothesize that intracellular glycation events occur in cardiac tissue that alter intermediary metabolism, particularly Ca2+ homeostasis, which leads to cell dysfunction. Additionally, we hypothesize that the high steady state intracellular concentrations of unphosphorylated creatine may offer protection against the formation of advanced glycation endproducts by reacting directly with glucose metabolites that may have reached toxic levels in the myocyte of diabetics.
University of Health Sciences, College of Osteopathic Medicine, Department of Biochemistry, Kansas City, Missouri 64124, USA.
P
P
Guichard
J E
JE
Burkhardt
N W
NW
Seidler
D001161:Arteriosclerosis / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D009202:Cardiomyopathies / Q000209:etiology* / Q000503:physiopathology; D003401:Creatine / Q000502:physiology*; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000503:physiopathology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008955:Models, Cardiovascular
D017127:Glycation End Products, Advanced; D003401:Creatine; D002118:Calcium