Myocardial glucose transporter GLUT1: translocation induced by insulin and ischemia

Myocardial glucose transport is not only facilitated by the insulin sensitive glucose transporter (GLUT) 4 but also by GLUT1. It was recently demonstrated that ischemia induces GLUT4 translocation by a mechanism distinct from the insulin-induced signaling pathway. However, the role of ischemia-mediated GLUT1 translocation and the signaling pathway involved is not yet defined. This study investigated the effects of wortmannin, a phosphatidylinositol-3 kinase (PI3kinase) inhibitor, on basal, ischemia- and insulin-stimulated GLUT1 redistribution. PI3kinase is known to participate in insulin-mediated GLUT4 translocation. Rat hearts were perfused with Krebs-Henseleit buffer containing 10 mmol/l glucose according to Langendorff and treated with/without 1 micromol/l wortmannin, 100 nmol/l insulin and 15 min no-flow ischemia. Relative subcellular distribution of GLUT1 protein was analysed using membrane fractionation and subsequent Western blotting. Both ischemia and insulin significantly increased the relative amount of GLUT1 in the plasma membrane (PM) compared to controls (41.6+/-2.8% in controls v 46.0+/-2.3% in ischemic and 51.4+/-3.9% in insulin hearts, both P<0.05) with a concomitant decrease of GLUT1 in intracellular membranes. However, the increases were moderate in view of the more than 2-fold stimulated GLUT4 translocation shown for ischemia and insulin. Although wortmannin completely inhibited insulin-induced GLUT1 translocation (42.0+/-2.0% GLUT1 on PM), it had no effect on the ischemia-induced translocation of GLUT1 (45. 4+/-1% GLUT1 on PM). Treatment with the inhibitor alone did not influence basal GLUT1 distribution. Results show that in the perfused rat heart, PI3 kinase is involved in the insulin-induced signaling leading to GLUT1 translocation but not in the ischemia-mediated signaling and basal GLUT1 trafficking. This suggests two different pathways for ischemia- and insulin-induced GLUT1 translocation as recently shown for GLUT4.