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Biochem Biophys Res Commun. 2008 Aug 8;372(4):639-43. doi: 10.1016/j.bbrc.2008.05.095. Epub 2008 Jun 2.

A novel membrane-based anti-diabetic action of atorvastatin.

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1
Department of Cellular & Integrative Physiology, Indiana University School of Medicine, Center for Diabetes Research, VanNuys Medical Science, Building Rm 308A, Indianapolis, IN 46202, USA.

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Abstract

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.

PMID:
18514061
PMCID:
PMC2505332
DOI:
10.1016/j.bbrc.2008.05.095
[Indexed for MEDLINE]
Free PMC Article
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