Glucose for the Aging Heart?

Abstract

Aging is associated with increased susceptibility of the heart to ischemia. Many potential reasons for this exist, including increased oxidative stress, mitochondrial dysfunction, and possibly changes in myocardial substrate utilization.1,2 Given the fact that ischemic heart disease is the leading cause of death in the aging population, strategies that increase the ability of the heart to recover after ischemic insults could have important therapeutic benefits. In a report published in this issue of Circulation , Luptak and colleagues describe the susceptibility of isolated hearts from mice with lifelong overexpression of the GLUT1 glucose transporter to ischemia and reperfusion.3 They report that a long-term increase in glucose utilization limits age-related diastolic dysfunction and is associated with a reduction in ischemic contracture during low-flow ischemia and improved recovery of systolic and diastolic function after reperfusion. Importantly, overexpression of the GLUT1 transgene was associated with reduced rates of depletion of cardiac ATP stores during ischemia that were particularly striking in young mice, higher concentrations of phosphocreatine at baseline in older mice, and a more rapid restoration of high-energy phosphate content in the hearts of young and old transgenic mice after reperfusion. Thus, maintaining high rates of myocardial glucose utilization might retard age-related myocardial dysfunction and promote functional recovery after ischemia. Article p 901 To maintain high rates of ATP generation, the heart exhibits a remarkable ability to metabolize a variety of metabolic substrates. It is widely accepted that under physiological circumstances, oxidative metabolism of fatty acids accounts for >50% of myocardial ATP generation in the nonstressed heart, with the remaining energy being derived from metabolism of lactate, ketone bodies, and glucose.4 Glucose entry into the heart is mediated via members of the facilitative glucose transporter family. This family has 12 members (GLUT1–12) with varying tissue distribution and subcellular localization. The …