A novel membrane-based anti-diabetic action of atorvastatin.
We recently found that chromium picolinate (CrPic), a nutritional supplement thought to improve insulin sensitivity in individuals with impaired glucose tolerance, enhances insulin action by lowering plasma membrane (PM) cholesterol. Recent in vivo studies suggest that cholesterol-lowering statin drugs benefit insulin sensitivity in insulin-resistant patients, yet a mechanism is unknown. We report here that atorvastatin (ATV) diminished PM cholesterol by 22% (P<0.05) in 3T3-L1 adipocytes. As documented for CrPic, this small reduction in PM cholesterol enhanced insulin action. Replenishment of cholesterol mitigated the positive effects of ATV on insulin sensitivity. Co-treatment with CrPic and ATV did not amplify the extent of PM cholesterol loss or insulin sensitivity gain. In addition, analyses of insulin signal transduction suggest a non-signaling basis of both therapies. Our data reveal an unappreciated beneficial non-hepatic effect of statin action and highlight a novel mechanistic similarity between two recently recognized therapies of impaired glucose tolerance.
Department of Cellular & Integrative Physiology, Indiana University School of Medicine, Center for Diabetes Research, VanNuys Medical Science, Building Rm 308A, Indianapolis, IN 46202, USA.
Emily M
EM
Horvath
Lixuan
L
Tackett
Jeffrey S
JS
Elmendorf
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000069059:Atorvastatin; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D051379:Mice; D010848:Picolinic Acids / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D010848:Picolinic Acids; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin; C030614:picolinic acid