Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Adipocytes / drug effects
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Adipocytes / metabolism*
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Aminopeptidases / drug effects
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Aminopeptidases / metabolism
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Animals
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Anticholesteremic Agents / pharmacology
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Caveolin 2
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Caveolins / drug effects
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Caveolins / genetics
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Caveolins / metabolism
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Cells, Cultured
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Cholesterol / metabolism
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Cystinyl Aminopeptidase
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Glucose Transporter Type 1
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Glucose Transporter Type 4
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
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Insulin Resistance*
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Lovastatin / pharmacology*
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Mevalonic Acid / pharmacology
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Mice
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Monosaccharide Transport Proteins / drug effects
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Monosaccharide Transport Proteins / metabolism*
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Muscle Proteins*
Substances
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Anticholesteremic Agents
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Caveolin 2
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Caveolins
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Glucose Transporter Type 1
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Glucose Transporter Type 4
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Monosaccharide Transport Proteins
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Muscle Proteins
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Slc2a1 protein, mouse
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Slc2a4 protein, mouse
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Cholesterol
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Lovastatin
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Aminopeptidases
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Cystinyl Aminopeptidase
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leucyl-cystinyl aminopeptidase
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Mevalonic Acid