Inhibition of isoprenoid biosynthesis causes insulin resistance in 3T3-L1 adipocytes.
Lovastatin treatment caused down-regulation of the insulin-responsive glucose transporter 4 (Glut4) and up-regulation of Glut1 in 3T3-L1 adipocytes. These changes in protein expression were associated with a marked inhibition of insulin-stimulated glucose transport. Lovastatin had no effect on cell cholesterol levels, but its effects were reversed by mevalonate, demonstrating that inhibition of isoprenoid biosynthesis causes insulin resistance in 3T3-L1 adipocytes. These findings support the notion that whole body insulin resistance may arise as a result of perturbations in general biochemical pathways, rather than primary defects in insulin signalling.
Chamberlain
L H
LH
Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, G12 8QQ, Glasgow, UK. l.chamberlain@bio.gla.ac.uk
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000626:Aminopeptidases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D051243:Caveolin 2; D022461:Caveolins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D010122:Cystinyl Aminopeptidase; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007333:Insulin Resistance; D008148:Lovastatin / Q000494:pharmacology*; D008798:Mevalonic Acid / Q000494:pharmacology; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D009124:Muscle Proteins
D000924:Anticholesteremic Agents; D051243:Caveolin 2; D022461:Caveolins; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495678:Slc2a1 protein, mouse; C495693:Slc2a4 protein, mouse; D002784:Cholesterol; D008148:Lovastatin; D000626:Aminopeptidases; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase; D008798:Mevalonic Acid