Cardiac Glucose Uptake and Suppressed Expression/Translocation of Myocardium Glucose Transport-4 in Dogs Undergoing Ischemia-Reperfusion

Abstract

Impaired glucose metabolism is implicated in cardiac failure during ischemia-reperfusion. This study examined cardiac glucose uptake and expression of glucose transport-4 (GLUT-4) in dogs undergoing ischemia-reperfusion. Cardiac ischemia was induced by cardiopulmonary bypass for 30 min or 120 min in dogs. Plasma insulin and glucose concentrations were measured at pre-bypass (control), and aortic cross-clamp off (ischemia-reperfusion) at 15, 45, and 75 min. At the same time, the left ventricle biopsies were taken for GLUT-4 immunohistochemistry and glycogen content analysis. In dogs receiving 120-min ischemia, coronary arterial and venous glucose concentrations were increased, but the net glucose uptake in ischemia-reperfusion heart were significantly decreased from 25% (control) to zero at 15 and 45 min of reperfusion, and recovered to only 7% after 75 min reperfusion. Myocardium glycogen contents were decreased by 65%. Plasma insulin levels and Insulin Resistant Index were markedly increased in dogs undergoing 120-min ischemia and reperfusion. These changes were relatively mild and reversible in dogs receiving only 30-min ischemia followed by reperfusion. Expression of total GLUT-4 in myocardium was decreased 40% and translocation of GLUT-4 from cytoplasm to surface membrane was decreased 90% in dogs receiving 120-min ischemia followed by 15-min reperfusion. Suppressed translocation of GLUT-4 was also evident in dogs receiving 30-min ischemia, but to a lesser extent. Reduced myocardium glucose uptake, utilization, and glycogen content are clearly associated with ischemia-reperfusion heart injury. This appears to be due, at least in part, to suppressed expression and translocation of myocardium GLUT-4.

Proteomic analysis of hepatic ischemia/reperfusion injury and ischemic preconditioning in mice revealed the protective role of ATP5β

“…Upon I/R injury, major enzymes involved in energy metabolism, methyl metabolism, lipid synthesis, and amino acid metabolism were downregulated, indicating a global impairment of metabolic activity in liver tissues, which might reflect an adaptive mechanism for the hepatocyte to reduce energy dissipation under a condition of ischemia and hypoxia. This observation is partially in accordance with a recent observation in ischemic heart that cardiac I/R injury are associated with reduced myocardium glucose uptake, utilization, and glycogen content [28]. It is worth mention that pretreated the mice with 10 min of ischemia and 10 min of reperfusion before I/R partly reversed the suppression of hepatic metabolic activity, suggesting a possible mechanism of the hepatoprotective effect of IPC.…”

Proteomics of Ischemia/Reperfusion Injury in Rat Intestine With and Without Ischemic Postconditioning

“…The current study showed that the expression of cytoplasmic aconitate hydratase was down-regulated by I/R, indicating a global impairment of metabolic activity and reduced energy dissipation in intestinal mucosa tissue. This observation was partially in accordance with a recent observation in ischemic heart, which showed that cardiac I/R injury was associated with reduced myocardium glucose uptake, utilization, and glycogen content [16]. It is worthy to mention that post-treatment of the rat with three cycles of reperfusion of SMA for 30 s followed by occlusion for 30 s between ischemia and reperfusion up-regulated the expression of cytoplasmic aconitate hydratase, which might be a potential mechanism whereby IPo conferred intestinal protection.…”

Exenatide Improves Glucose Homeostasis and Prolongs Survival in a Murine Model of Dilated Cardiomyopathy

“…The current findings may also have physiologic relevance to other situations such as the ischemic heart, which loses its normal substrate flexibility and becomes more dependent upon glucose as a metabolic fuel [28]. Finally, the ultimate question is whether the survival benefit of exenatide in a murine model will translate to human patients.…”