EFFECT OF INSULIN ON GLUCOSE OXIDATION IN VASCULAR SMOOTH MUSCLE CELLS.† 556

Abstract

Glucose metabolism in vascular smooth muscle (VSM) is characterized by production of lactic acid rather than pyruvate oxidation (Am J Physiol 1995). An increase in aerobic lactate production by VSM may result in lactic acidosis in certain vascular diseases such as hypertension and atherosclerosis. Activation of pyruvate dehydrogenase (PDH) by insulin in adipocytes and fibroblasts increases pyruvate oxidation and decreases lactate oxidation in the presence of glucose. Experiments were designed to determine if insulin would divert glucose metabolism in VSM cells from lactate production to pyruvate oxidation. Lactate oxidation was determined in control VSM cells cultured from rat aortic tissue and incubated in media without insulin or glucose (9.6 ± 2.4 μmol/1×106 cells/min) by measuring the conversion of [1-14C]-D,L-lactate to [1-14C]-pyruvate and the subsequent oxidation to acetyl CoA and 14CO2 by PDH. Lactate oxidation measured in VSM cells with glucose alone (4.6 ± 1.7μmol/1×106 cells/min) was decreased compared to control(p<0.001). Insulin alone (100 μU/ml) induced [1-14C]-D,L-lactate oxidation in VSM cells (17.9 ± 4.4 μmol/1×106 cells/min) and was greater than both control (p< 0.01) and glucose alone(p< 0.001). However, unlike in adipocytes and fibroblasts, lactate oxidation did not decrease in VSM when insulin and glucose were both added to the media (12.9 ± 1.56 μmol/1×106 cells/min). This suggests that insulin does not divert glucose from lactate production to generate pyruvate in VSM but instead may utilize lactate as a source of pyruvate and energy production even during noncontractile periods.