Postnatal increase in insulin-sensitive glucose transporter expression is associated with improved recovery of postischemic myocardial function

Abstract

Objective: Glucose is an important substrate for energy production in the developing heart. Increased glucose uptake rate and metabolism during ischemia and reperfusion are closely linked to postischemic myocardial recovery. The initial rate-limiting step for glycolysis is the transport of glucose across the plasma membrane by glucose transporters (GLUT-1 and GLUT-4). We hypothesized that changes in GLUT-1 and GLUT-4 expression in developing hearts lead to age-dependent adaptive changes in glucose uptake capacity and influence tolerance to ischemia. Methods: Western-immunoblotting was performed to determine GLUT-1 and GLUT-4 expression in myocardial tissue from 1, 2, and 3-week-old and adult rabbits. Glucose uptake rate was measured with 31P-nuclear magnetic resonance spectroscopy using 2-deoxyglucose as substrate in isolated perfused hearts. Hearts from same age rabbits were perfused in the Langendorff mode with crystalloid buffer or buffer plus a GLUT-4 specific antibody in order to determine GLUT-4 mediated effects on myocardial protection. The hearts were subjected to 30 minutes of normothermic ischemia followed by reperfusion. Cardiac contractile function measurements were obtained pre- and postischemia. Tissue lactate accumulation was measured in all groups at end-ischemia. Conclusions: Insulin-regulated glucose transporter (GLUT-4) expression in the heart increased gradually after birth reaching nearly adult levels by 3 weeks of age. Corresponding with the higher amount of GLUT-4 protein, improved recovery of postischemic contractile function was seen in older hearts in association with increased anaerobic glycolytic capacity. Interventions to accelerate postnatal GLUT-4 expression may improve ischemic tolerance in the neonatal heart.