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Departments of 1Kinesiology and 2Physiology and 3Groupe de Recherche sur le Système Nerveux Autonome, University of Montreal, Montreal, Quebec H3C 3J7; 4Montreal Heart Institute, Montreal, Quebec H1T 1C8; 5Neuroscience Research Group and 6Département de Chimie-Biologie, Université du Québec à Trois-Rivières, Trois-Rivières, Quebec G9A 5H7; and 7Department of Human Kinetics, Laurentian University, Ontario, Canada P3E 2C6
Submitted 12 August 2003 ; accepted in final form 22 December 2003
Cardiac dysfunction is a severe secondary effect of Type 2 diabetes. Recruitment of the protein kinase B/glycogen synthase kinase-3 pathway represents an integral event in glucose homeostasis, albeit its regulation in the diabetic heart remains undefined. Thus the following study tested the hypothesis that the regulation of protein kinase B/glycogen synthase kinase-3 was altered in the myocardium of the Zucker diabetic fatty rat. Second, exercise has been shown to improve glucose homeostasis, and, in this regard, the effect of swimming training on the regulation of protein kinase B/glycogen synthase kinase-3 in the diabetic rat heart was examined. In the sedentary Zucker diabetic fatty rats, glucose levels were elevated, and cardiac glycogen content increased, compared with wild type. A 13-wk swimming regimen significantly reduced plasma glucose levels and cardiac glycogen content and partially normalized protein kinase B-serine473, protein kinase B-threonine308, and glycogen synthase kinase-3
phosphorylation in Zucker diabetic fatty rats. In conclusion, hyperglycemia and increased cardiac glycogen content in the Zucker diabetic fatty rats were associated with dysregulation of protein kinase B/glycogen synthase kinase-3 phosphorylation. These anomalies in the Zucker diabetic fatty rat were partially normalized with swimming. These data support the premise that exercise training may protect the heart against the deleterious consequences of diabetes.
diabetes; Type 2; glycogen; heat shock protein
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