Effects of insulin and metformin on glucose metabolism in rat vascular smooth muscle

Glucose metabolism in vascular smooth muscle cells (VSMCs) is characterized by substantial lactate production even in fully oxygenated conditions. Ins ulin and metformin, an insulin-sensitizing agent, have direct effects on th e vascular tissue metabolism. We investigated whether insulin or metformin can induce a switch in VSMC glucose metabolism from lactate production to p yruvate oxidation, by measuring lactate oxidation as determined by the conv ersion of [1-C-14]-D,L-lactate to [1-C-14]-pyruvate and subsequent oxidatio n to acetyl coenzyme A and (CO2)-C-14 by pyruvate dehydrogenase (PDH). Lact ate oxidation was measured in control rat aortic cultured VSMCs incubated f or 30 minutes in media with and without additional glucose compared with VS MCs cultured in the presence of insulin or metformin. The addition of gluco se to VSMCs decreased lactate oxidation (4.6 +/- 1.7 v 9.6 +/- 2.4 pmol/cel l/min, P < .001). In the absence of additional glucose, metformin decreased lactate oxidation in VSMCs compared with controls (4.9 +/- 1.4 v 9.6 +/- 2 .4 pmol/cell/min, P < .01). Metformin in the presence of glucose caused the greatest decline in lactate oxidation (2.5 +/- 0.4 pmol/cell/min, P < .001 ). In contrast to the effects of metformin, insulin increased lactate oxida tion bath with (12.9 +/- 1.5 pmol/cell/min, P < .001) and without (17.9 +/- 4.4, P < .01) additional glucose. This suggests that insulin facilitates V SMC: utilization of lactate as a source of pyruvate and energy production e ven during noncontractile periods, Copyright (C) 1999 by W.B. Saunders Comp any.