OBJECTIVETo investigate the molecular mechanism of the effect of alcohol on insulin sensitivity.

METHODSFour groups of Wistar rats were used, i.e. control (C) group, and low (L), moderate (M) and high (H) alcohol group. Alcohol doses of each group were 0, 0.6, 1.8 and 3.0 ml.(kg.bw)(-1).day(-1). Each group was comprised of 10 male and 10 female rats. Alcohol was given to rats by gastric intubation. Thirteen weeks later, serum was collected for testing of fasting plasma glucose and insulin. HOMA-IR index of each group were calculated. Total muscle RNA was extracted using Trizol Reagent (Promega). The expression level of IRS-1 mRNA in muscle was detected by RT-PCR.

RESULTSIn female rats, the fasting plasma glucose of group (8.36 +/- 0.57) mmol/L was higher and the fasting plasma insulin (15.25 +/- 3.32) was lower than those of group C (7.56 +/- 0.85, 20.80 +/- 3.25). The HOMA-IR of group L (1.775 3 +/- 0.138 1) was lower than that of group C (1.982 6 +/- 0.124 6) (P < 0.05), while IRS-1 mRNA (0.766 1 +/- 0.076 9) was up-regulated (P < 0.05); HOMA-IR of group M (2.202 2 +/- 0.271 0) was higher than that of group C (P < 0.01), while IRS-1 mRNA (0.501 8 +/- 0.049 2) was suppressed (P < 0.01); HOMA-IR of group H (1.850 1 +/- 0.162 8) was not significantly changed as compared with that of group C (1.982 6 +/- 0.124 6) (P > 0.05), while IRS-1 mRNA (0.418 1 +/- 0.049 1) was significantly suppressed (P < 0.01). In male rats, the fasting plasma glucose and insulin had the similar change as those of female rats. The HOMA-IR of group M (1.878 5 +/- 0.250 2) was lower than that of C group (2.147 3 +/- 0.330 8) (P < 0.05), IRS-1 mRNA was up-regulated (0.824 9 +/- 0.064 7) (P < 0.05).

CONCLUSIONSThe present study showed that low-to-moderate dose of alcohol could increase insulin sensitivity; while alcohol abuse could decrease insulin sensitivity. Sex difference in this effect was found. Changes of IRS-1 mRNA expression may be involved in the molecular mechanism of the effects of alcohol on insulin sensitivity.