[Study on the mechanism of insulin resistance in rats born with intrauterine growth retardation].

ABSTRACT

OBJECTIVE: To investigate the expressions of the insulin receptor (IR), insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), phosphatidyl inositol 3-kinase (PI3K) and insulin-like growth factor-1 (IGF-1) of the livers of the male adult rats born with intrauterine growth retardation (IUGR),and to find out the relationship between IUGR and insulin resistance in their adult life. METHODS: The foods were available ad libitum throughout the pregnancy to the control group and the rats in the experimental group were fed 50% of the control group to build the IUGR animal model. Liver samples were collected when the male offspring grew up to 12 weeks old. The mRNA expressions of hepatic IR, IRS-1, IRS-2, PI3K, and IGF-1 were detected by RT-PCR. The protein expressions of hepatic IR, IRS-1, and IRS-2 were analyzed by immunohistochemistry. RESULTS: The mRNA expressions of hepatic IR in the adult male rats with IUGR were significantly lower than control group [(0.41+/-0.06) vs (0.62+/-0.11), P<0.05]. But the expressions of hepatic IR protein were similar [(6.21+/-0.57) vs (6.69+/-0.47), P>0.05] in both groups. The mRNA and protein expressions of the hepatic IRS-1 [mRNA (0.77+/-0.20) vs (1.32+/-0.42), P<0.05; protein (2.15+/-0.23) vs (5.96+/-0.38), P<0.05] and IRS-2 [mRNA (1.05+/-0.28) vs (1.48+/-0.40), P<0.05; protein (4.33+/-0.29) vs (7.08+/-0.35), P<0.05] of the IUGR rats were reduced; there were no differences between the hepatic PI3K mRNA expressions in the 2 groups [(1.12+/-0.19) vs (1.18+/-0.24), P>0.05]. The expressions of hepatic IGF-1 mRNA of the rats with IUGR were significantly lower than those in control group [(0.55+/-0.12) vs (1.22+/-0.34), P<0.05]. There was close relation between the reduction of the expression of hepatic IGF-1 mRNA and the expression of IRS-1 mRNA (r=0.821, P<0.05) and IRS-2 mRNA(r=0.643, P<0.05) in the adult male rats with IUGR. CONCLUSION: The reduced expressions of IRS-1 and IRS-2 caused the lower expression of hepatic IGF-1 in the adult male rats with IUGR, which was related to the stunted growth and the insulin resistance. There were no relation of the expressions of hepatic IR and PI3K and the insulin resistance in adult male rats with IUGR.