[Effect of chronic ethanol intake on insulin receptor, insulin receptor subsrate-1 and phosphoinositide 3-kinase mRNA expression in skeletal muscle of rats]

Abstract

Objective: To study the effect of chronic ethanol intake on insulin receptor (IR), insulin receptor substrate-1 (IRS-1) and p85 subunit of phosphoinositide 3-kinase (PI-3K) mRNA expression in skeletal muscle of rats and explore the molecular mechanism of ethanol induced insulin resistance.

Methods: 80 Wistar rats were randomly divided into four groups on the basis of body weight: control (C) group, low (L), moderate (M) and high (H) ethanol group. Each group was comprised of 10 male and 10 female rats. Rats were given ethanol in different concentration of (10%, 20% and 33%) through intragastric-feeding and ethanol doses was 10 ml/kg bw per day. After 19 weeks treatment, fasting plasma glucose and insulin were measured. HOMA-IR index of each group were calculated. The expression of IR, IRS-1 and PI-3K (p85) mRNA in skeletal muscle were detected by RT-PCR.

Results: In male rats, the fasting plasma glucose of group H, fasting plasma insulin of group L, M and HOMA-IR indexes of all ethanol-fed groups were higher than those of group C (P < 0.05). The levels of IR mRNA of group L and H was lower, while increasing with the ethanol doses, IRS-1 and PI-3K(p85) mRNA expression increased first, then was decreased (P < 0.05). In female rats, in comparation with group C, the fasting plasma glucose of group H was higher, while fasting plasma insulin was lower, the levels of IR, IRS-1, PI-3K(p85) mRNA of group H and M were suppressed (P < 0.05). HOMA-IR indexes had on differences in the four groups of female rats (P > 0.05).

Conclusion: The present results suggested that chronic ethanol intake could induce insulin resistance and down-regulated the expression of IR, IRS-land PI-3K mRNA in skeletal muscle could be the molecular mechanism.