INSULIN AND INSULIN-LIKE GROWTH-FACTOR-I MODULATION OF GLUCOSE-TRANSPORT IN ARTERIAL SMOOTH-MUSCLE CELLS - IMPLICATION OF GLUT-4 IN THE VASCULATURE

Insulin modulates many physiological processes in vascular smooth muscle cells (VSMC) such as contractility, proliferation, and ion homeostasis. However, hormonal modulation of glucose transport has not been explored in pure populations of these cells. This study demonstrates that insulin and insulin-like growth factor-1 (IGF-1) increase glucose transport in a7r5 clonal and freshly prepared Sprague-Dawley aortic (SDa) VSMC. In a7r5 cells, physiologic (10(-12) to 10(-9) mol/L) insulin concentrations increase transport by 8% to 15%, whereas supraphysiologic concentrations (10(-9) to 10(-6) mol/L) increase transport by up to 60% (P < .05 v no increase over all concentrations tested). In SDa cells, insulin was more potent, displaying maximum transport stimulation of 70% at 10(-8) mol/L (P < .05 v a7r5 cells). Insulin regulation of glucose transport occurs by a protein synthesis-independent pathway as 10 mu mol/L cycloheximide was without effect. Insulin produces these effects within 20 min of treatment, and cytochalasin B (10 mu mol/L) inhibits both basal and insulin-stimulated glucose transport by 93% and 96%, respectively. Stimulation of insulin receptors alone, with 2.5 pg/mL insulin receptor-specific antibody, stimulates glucose transport by 20%, suggesting transport can be stimulated by an IGF-1 receptor independent mechanism. However, IGF-1 is a more potent stimulator of transport in both cell lines studied, with maximal stimulation (10(-8) mol/L IGF-1) of 60% and 80% in a7r5 and SDa cells, respectively (P < .05 v 10(-8) mol/L insulin in both cell lines). Insulin stimulation of glucose transport is specific for [D+]-glucose; [L-]-glucose does not compete for transport. Our preliminary antibody staining experiments in a7r5 cells, as well as previously reported data on A-10 VSMC, indicate that these (identical) cell lines possess the insulin-sensitive GLUT-4 transporter. Hormonal control of glucose transport (including a possible autocrine effect of IGF-1) may help explain abnormalities in VSMC proliferation, contractility, and ion homeostasis as seen in diabetic hypertension and atherosclerosis.