Biphasic effects of chronic ethanol exposure on insulin-stimulated glucose uptake in primary cultured rat skeletal muscle cells: role of the Akt pathway and GLUT4
✍ Scribed by Wei Qu; Lina Zhao; Xiaolin Peng; Xuefeng Yang; Chenjiang Ying; Liping Hao; Xiufa Sun
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 215 KB
- Volume
- 27
- Category
- Article
- ISSN
- 1520-7552
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✦ Synopsis
Abstract
Background
Mild or moderate chronic alcohol intake has been shown to be associated with increased insulin sensitivity, while chronic alcohol abuse demonstrates a contrary effect. The mechanism underlying this biphasic effect has not yet been clarified. We investigated whether chronic ethanol exposure mediates biphasic changes on insulin sensitivity and whether the phosphatidylinositol 3‐kinase/Akt pathway is involved in vitro.
Methods
Primary cultured rat skeletal muscle cells were exposed to ethanol (0–400 mM) for 24 h. Insulin sensitivity was assessed by the ^3^H‐labelled 2‐deoxyglucose uptake assay.
Phosphatidylinositol 3‐kinase, cytosol and cell membrane glucose transporter‐4 (GLUT4), as well as the Akt phosphorylated form, were analyzed by Western blots.
Results
Biphasic effects of ethanol on insulin sensitivity were observed in primary cultured skeletal muscle cells in a dose‐dependent manner. Compared with the untreated group, 50 and 100 mM concentrations of ethanol resulted in a significant increase in 2‐deoxyglucose uptake by 29 and 28%, respectively, while higher concentrations of ethanol (200, 400 mM) showed a significant decrease in 2‐deoxyglucose uptake by 28 and 47%, respectively. The changes in glucose transport activity were in line with the changes in Akt Ser473 phosphorylation and GLUT4 expression in an ethanol dose‐dependent biphasic manner. The phosphorylation of Akt and GLUT4 protein contents were up‐regulated after treatment with low concentrations of ethanol (50, 100 mM) and down‐regulated with high concentrations of ethanol (200, 400 mM) for 24 h.
Conclusion
Ethanol mediates biphasic changes on insulin sensitivity at least in part via the Akt pathway and GLUT4 expression. Copyright © 2010 John Wiley & Sons, Ltd.