New insights into myocardial glucose metabolism: surviving under stress

PURPOSE OF REVIEW: Myocardial glucose uptake and metabolism are essential for maintaining myocardial energetics under circumstances of stress, such as myocardial ischemia or hypertrophy. We will discuss new information as to the mechanisms of altered glucose uptake as a consequence of impaired insulin action as well as emerging alternative cellular signaling mechanisms that lead to increased noninsulin dependent glucose uptake and metabolism. We will also review provocative clinical data that demonstrate the limitations of tight glycemic control as a mechanism to confer myocardial protection in patients with type 2 diabetes and discuss potential mechanistic explanations for the paradoxical results. RECENT FINDINGS: New studies have shed important light on the distal mechanisms involved in insulin-mediated Glut 4 translocation. There are also important new insights into the role of AMP kinase and hypoxia-induced factor-1alpha in mediating myocardial glucose uptake while conferring cardioprotection. SUMMARY: The importance of understanding the link between glucose uptake and cardioprotection is underscored by recent clinical trials that have failed to demonstrate a benefit between tight glycemic control and reduced cardiovascular events. These data underscore the need for additional agents that affect both outcomes.