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. Insulin and metformin, an insulin-sensitizing agent, have direct effects on the vascular tissue metabolism. We investigated whether insulin or metformin can induce a switch in VSMC glucose metabolism from lactate production to pyruvate oxidation, by measuring lactate oxidation as determined by the conversion of [1-14C]-D,L-lactate to [1-14C]-pyruvate and subsequent oxidation to acetyl coenzyme A and 14CO2 by pyruvate dehydrogenase (PDH). Lactate oxidation was measured in control rat aortic cultured VSMCs incubated for 30 minutes in media with and without additional glucose compared with VSMCs cultured in the presence of insulin or metformin. The addition of glucose to VSMCs decreased lactate oxidation (4.6+/-1.7 v 9.6+/-2.4 pmol/cell/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 oxidation both 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 VSMC utilization of lactate as a source of pyruvate and energy production even during noncontractile periods.
Ofenstein
J P
JP
Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA.
Dominguez
L J
LJ
Sowers
J R
JR
Sarnaik
A P
AP
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000818:Animals; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D007004:Hypoglycemic Agents; D007328:Insulin; D011768:Pyruvate Dehydrogenase Complex; D019344:Lactic Acid; D000105:Acetyl Coenzyme A; D019289:Pyruvic Acid; D008687:Metformin; D005947:Glucose