Additive Effects of Hyperinsulinemia and Ischemia on Myocardial GLUT1 and GLUT4 Translocation In Vivo

Abstract

Background-Myocardial ischemia increases glucose uptake through the translocation of GLUT1 and GLUT4 from an intracellular compartment to the sarcolemma. The present study was performed to determine whether hyperinsulinemia causes translocation of myocardial GLUT1 as well as GLUT4 in vivo and whether there are additive effects of insulin and ischemia on GLUT1 and GLUT4 translocation. Methods and Results-Myocardial glucose uptake and transporter distribution were assessed by arteriovenous measurements, cell fractionation, and immunofluorescence. In fasted anesthetized dogs, hyperinsulinemia increased myocardial glucose extraction 3-fold (PϽ0.01) and the sarcolemmal content of GLUT4 by 90% and GLUT1 by 50% (PϽ0.05 for both) compared with saline infusion. In subsequent experiments, glucose uptake and transporter distribution were determined in ischemic and nonischemic regions of hearts from hyperinsulinemic animals during regional myocardial ischemia. Glucose uptake was 50% greater in the ischemic region (PϽ0.05). This was associated with a 20% increase in sarcolemmal GLUT1 and a 60% increase in sarcolemmal GLUT4 contents in the ischemic region (PϽ0.05 for both). Conclusions-Insulin stimulates myocardial glucose utilization through translocation of GLUT1 as well as GLUT4.Insulin and ischemia have additive effects to increase in vivo glucose utilization and augment glucose transporter translocation. We conclude that recruitment of both GLUT1 and GLUT4 contributes to increased myocardial glucose uptake during moderate reductions in coronary blood flow under insulin-stimulated conditions. (Circulation. 1998;98:2180-2186.)

Increased Adenosine Monophosphate–Activated Protein Kinase Activity in Rat Hearts With Pressure-Overload Hypertrophy

“…7,24,28 This is supported by the observation that there is an additive effect of AMPK activation or ischemia to insulin-stimulated glucose uptake. 7,28,29 In the present study, however, glucose uptake during insulin stimulation was similar for hearts with low AMPK activity (control) and hearts with high AMPK activity (LVH). This may result from decreased total GLUT4 content in LVH, which limits the capacity for GLUT4-mediated glucose transport.…”

Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heart

“…This contrasts with adipose tissue and skeletal muscle, in which GLUT4 is the major mediator of basal glucose uptake (17)(18)(19). Insulin induces translocation of the GLUT1 transporter in the heart in vivo (13,52), in primary rat adipocytes (17), and in 3T3L1 adipocytes (53). GLUT1 also translocates to the plasma membrane in the heart in response to ischemia (14).…”

Impaired insulin-signaling in hypertrophied hearts contributes to ischemic injury

“…Brosius et al [43] did not find that ischemia in the presence of insulin resulted in additional GLUT-4 translocation. However, when hyperinsulinemia was present, Russell et al [44] reported an increase in GLUT-4 as well as GLUT-1 translocation rate. If indeed alternate pathways regulate ischemia-induced GLUT-4 regulation as effectively as insulin-mediated GLUT-4 activation, then we could show in this study that in hypertrophied hearts not only insulin-regulated glucose uptake is impaired but ischemia as additional stimulus for GLUT-4 translocation did not ameliorate this effect.…”