Chronic alcohol exposure induces insulin resistance in mice : the possible mechanism of ceramide

Abstract

Objective To investigate the relationship among chronic alcohol exposure,insulin sensitivity and ceramide during the alcohol toxicological effect. Methods Wide type( WT) and sphingomyelin synthetase 2 knockout( SMS- /-2) mice( about 3 month old) were used to establish the chronic alcohol exposure model. A total of 90 mice of the two genotypes were divided into the control group,moderate EtOH group and high EtOH group. After alcohol exposure for5 months,fasting plasma glucose( FPG) and levels of fasting insulin( Fins) were measured. The insulin resistance index( HOMA-IR) was calculated. The expression of insulin receptor substrate 2( IRS2) in hippocampus was tested with immunofluorescent labeling and Western blotting analysis. Results 1. Alcohol exposure caused WT mice FPG and HOMA-IR index increased with dose-dependency( P 0. 05). Comparing with the control group,Fins values increased in the treatment dose group( P 0. 05). 2. FPG in SMS- /-2mice increased with dose-dependency( P 0. 05),but HOMAIR index had little changes,comparing with WT mice. In addition,the immunohistochemical staining showed that,in both WT and SMS- /-2mice,the number of IRS2-positive cells reduced in CA1 area after alcohol exposure with dose-dependency( P 0. 05). However,comparing with the WT mice,the number of IRS2-positive cells of hippocampus in SMS- /-2mice reduced greatly( P 0. 05). 3. Immunoblotting evidence of IRS2 supported the results of immunohistochemistry in bothWT and SMS- /-2mice. Conclusion Chronic alcohol exposure can cause insulin resistance in both WT and SMS- /-2mice.IRS2 protein expression decreased with dose-dependency after alcohol exposure. IRS2 loss probably is one of the causes of insulin resistance. Ceramide may be involved in the reduction of IRS2 expression and may promote the formation of insulin resistance after alcohol exposure.