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Impaired cardiac glucose uptake and utilization, and suppressed expression/translocation of myocardium glucose transport-4 in dogs undergoing ischemia-reperfusion

¹ Affiliated Hospital of Zunyi Medical College

^* To whom correspondence should be addressed. E-mail: guiyou515{at}163.com.

	Abstract

Background: Impaired glucose metabolism is implicated in cardiac failure during ischemia-reperfusion. Objective: This study examined cardiac glucose uptake and expression of glucose transport-4 (GLUT-4) in dogs undergoing ischemia-reperfusion. Methods: 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. Results: In dogs receiving 120-min ischmia, 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. Conclusions: 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.

Key Words: Cardiopulmonary bypass, dog, myocardial glucose uptake, insulin resistance, glucose transport-4, ischemia-reperfusion