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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 639-643 |
| Number of pages | 5 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 372 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 8 2008 |
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Keywords
- Atorvastatin
- Cholesterol
- GLUT4
- Insulin
- Insulin resistance
- Plasma membrane
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
A novel membrane-based anti-diabetic action of atorvastatin. / Horvath, Emily M.; Tackett, Lixuan; Elmendorf, Jeffrey S.
In: Biochemical and Biophysical Research Communications, Vol. 372, No. 4, 08.08.2008, p. 639-643.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A novel membrane-based anti-diabetic action of atorvastatin
AU - Horvath, Emily M.
AU - Tackett, Lixuan
AU - Elmendorf, Jeffrey S.
PY - 2008/8/8
Y1 - 2008/8/8
N2 - 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.
AB - 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.
KW - Atorvastatin
KW - Cholesterol
KW - GLUT4
KW - Insulin
KW - Insulin resistance
KW - Plasma membrane
UR - http://www.scopus.com/inward/record.url?scp=45449087250&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=45449087250&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2008.05.095
DO - 10.1016/j.bbrc.2008.05.095
M3 - Article
C2 - 18514061
AN - SCOPUS:45449087250
VL - 372
SP - 639
EP - 643
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -