%0 Journal Article
%T Impairment of insulin-stimulated Akt/GLUT4 signaling is associated with cardiac contractile dysfunction and aggravates I/R injury in STZ-diabetic Rats
%A Jiung-Pang Huang
%A Shiang-Suo Huang
%A Jen-Ying Deng
%A Li-Man Hung
%J Journal of Biomedical Science
%D 2009
%I BioMed Central
%R 10.1186/1423-0127-16-77
%X Diabetes mellitus is the world's fastest-growing disease with high morbidity and mortality rates predominantly as results of cardiovascular diseases [1,2]. Prospective studies have documented increased likelihood of sudden cardiac death and unrecognized myocardial infarctions in patients with diabetes [3]. Moreover, acute ischemic syndromes, peripheral arterial disease, and advanced cardiovascular disease (CVD) complications occur more commonly in patients with diabetes than in those without [3]. Despite the prevalence and the significant impact this disease has on our world today, the understanding of the cellular and molecular perturbations that predispose to altered myocardial structure and function remains incomplete. Recently, it has been speculated that myocardial insulin resistance develops in animal models of both type 1 and type 2 diabetes [4]. Various studies to date indicate multiple sites of impaired insulin signaling in various animal models; all the findings clearly support the existence of myocardial insulin resistance [4]. Insulin-stimulated glucose uptake, protein synthesis and glycogen synthesis have been shown to be reduced in the heart and cardiomyocytes of diabetic rats [5,6].Insulin regulates metabolism in the heart by modulating glucose transport, glycolysis, glycogen synthesis, lipid metabolism, protein synthesis, growth, contractility, and apoptosis in cardiomyocytes [7-9]. In addition, vasodilator actions of insulin in coronary vasculature augment myocardial perfusion [10]. As in other insulin-sensitive tissues, insulin signaling via PI3K/Akt pathways plays a key role in cardiac glucose uptake [7]. Insulin resistance is an important risk factor for the development of hypertension, atherosclerotic heart disease, left ventricular hypertrophy and dysfunction, and heart failure [11]. It reflects a disturbance of glucose metabolism and can potentially worsen metabolic efficiency of cardiomyocytes. During insulin resistance or diabetes, the heart
%U http://www.jbiomedsci.com/content/16/1/77