title: Coenzyme Q10 ameliorates the reduction in GLUT4 transporter expression induced by simvastatin in 3T3-L1 adipocytes.
abstract: BACKGROUND
  Statins significantly reduce cardiovascular events in a broad population of patients with hyperlipidemia. However, a small, but significant risk of new-onset diabetes has been reported in patients treated with statins. The mechanism by which statins cause diabetes has not been elucidated and therefore preventive strategies have yet to be defined.
  
  
  METHODS
  Our goal was to study the differing effects of a lipophilic (simvastatin) statin, hydrophilic (pravastatin) statin, and ezetimibe on glucose transporter-4 (GLUT4) protein expression in 3T3-L1 adipocytes. We hypothesized that the reductions in GLUT4 protein secondary to statin treatment would be prevented when cells were co-incubated with coenzyme Q10 (CoQ10). GLUT4 protein expression was determined using the In-Cell Western technique. Confluent adipocytes were differentiated using a hormonal cocktail for 3 days; followed by treatment with simvastatin, pravastatin, ezetimibe and CoQ10. Cell morphology was observed after treatment using phase-contrast microscopy.
  
  
  RESULTS
  Treatment with simvastatin (P<0.001) and simvastatin plus ezetimibe (P<0.001) significantly decreased GLUT4 protein expression in the adipocytes compared to control conditions. GLUT4 protein levels were similar to control after treatment with ezetimibe alone (P=0.52) or pravastatin (P=0.32). There was no significant difference (P=0.098) in GLUT4 protein levels after co-treatment with CoQ10 between any of the treatments and control conditions.
  
  
  CONCLUSIONS
  Our studies have shown that lipophilic statins (simvastatin) reduce the GLUT4 protein levels in adipocytes, whereas hydrophilic statins (pravastatin) or ezetimibe do not. Co-treatment with CoQ10 appears to prevent the reduction in GLUT4 protein levels caused by simvastatin.
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, Oregon State University/ Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Shobana
authors.initials: S
authors.lastname: Ganesan
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Ito
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001384:Azetidines / Q000008:administration & dosage / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000517:prevention & control; D004347:Drug Interactions; D000069438:Ezetimibe; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007333:Insulin Resistance; D051379:Mice; D017035:Pravastatin / Q000008:administration & dosage / Q000494:pharmacology; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D051275:Glucose Transporter Type 4; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C495693:Slc2a4 protein, mouse; D014451:Ubiquinone; D019821:Simvastatin; C024989:coenzyme Q10; D000069438:Ezetimibe; D017035:Pravastatin