Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 372, Issue 4, Pages 639-643Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.05.095
Keywords
atorvastatin; cholesterol; GLUT4; insulin; insulin resistance; plasma membrane
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Funding
- NCCIH NIH HHS [R01 AT001846, R01 AT001846-04, F31-AT003977-01] Funding Source: Medline
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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. (C) 2008 Elsevier Inc. All rights reserved.
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