IGF-I promotes a shift in metabolic flux in vascular smooth muscle cells.
13C-nuclear magnetic resonance (NMR) spectroscopy was used to test our hypothesis that insulin-like growth factor I (IGF-I) stimulates glucose flux into both nonoxidative and oxidative pathways in vascular smooth muscle cells (VSMC). Rat VSMC were exposed to uniformly labeled [13C]glucose ([U-13C]glucose; 5.5 mM) and [3-13C]pyruvate (1 mM) in the presence and absence of IGF-I (100 ng/ml). IGF-I increased glucose flux through glycolysis and the tricarboxylic acid (TCA) cycle as well as total anaplerotic flux into the TCA cycle. Previous work in our laboratory identified an increase in GLUT1 content and glucose metabolism in neointimal VSMC that was sufficient to promote proliferation and inhibit apoptosis. To test whether IGF-I could potentiate the GLUT1-induced increased flux in the neointima, we utilized VSMC harboring constitutive overexpression of GLUT1. Indeed, IGF-I markedly potentiated the GLUT1-induced increase in glucose flux through glycolysis and the TCA cycle. Taken together, these findings demonstrate that upregulation of glucose transport through either IGF-I or increased GLUT1 content stimulates glucose flux through both nonoxidative and oxidative pathways in VSMC.
Hall
Jennifer L
JL
Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia 30310, USA. Hallx068@umn.edu
Gibbons
Gary H
GH
Chatham
John C
JC
D000818:Animals; D002460:Cell Line; D002952:Citric Acid Cycle / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1; D006019:Glycolysis / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009004:Monosaccharide Transport Proteins / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495679:Slc2a1 protein, rat; D007334:Insulin-Like Growth Factor I; D019289:Pyruvic Acid; D005947:Glucose