Liao Yan, Li Hai Qi, Deng Bing, Qu Ping
Department of Child Health Care, Children's Hospital of Chongqing University of Medical Sciences, Chongqing, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2008 Dec 18;40(6):590-4.
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.
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.
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.
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.
研究宫内生长受限（IUGR）成年雄性大鼠肝脏中胰岛素受体（IR）、胰岛素受体底物-1（IRS-1）、胰岛素受体底物-2（IRS-2）、磷脂酰肌醇3激酶（PI3K）和胰岛素样生长因子-1（IGF-1）的表达情况，以探讨IUGR与成年后胰岛素抵抗之间的关系。
对照组大鼠在整个孕期自由进食，实验组大鼠给予对照组50%的食物量以建立IUGR动物模型。雄性子代大鼠长至12周龄时采集肝脏样本。采用逆转录聚合酶链反应（RT-PCR）检测肝脏IR、IRS-1、IRS-2、PI3K和IGF-1的mRNA表达。采用免疫组织化学法分析肝脏IR、IRS-1和IRS-2的蛋白表达。
IUGR成年雄性大鼠肝脏IR的mRNA表达显著低于对照组[（0.41±0.06）对（0.62±0.11），P<0.05]。但两组肝脏IR蛋白表达相似[（6.21±0.57）对（6.69±0.47），P>0.05]。IUGR大鼠肝脏IRS-1的mRNA和蛋白表达均降低[mRNA：（0.77±0.20）对（1.32±0.42），P<0.05；蛋白：（2.15±0.23）对（5.96±0.38），P<0.05]，IRS-2的mRNA和蛋白表达也降低[mRNA：（1.05±0.28）对（1.48±0.40），P<0.05；蛋白：（4.33±0.29）对（7.08±0.35），P<0.05]；两组肝脏PI3K的mRNA表达无差异[（1.12±0.19）对（1.18±0.24），P>0.05]。IUGR大鼠肝脏IGF-1的mRNA表达显著低于对照组[（0.55±0.12）对（1.22±0.34），P<0.05]。IUGR成年雄性大鼠肝脏IGF-1的mRNA表达降低与IRS-1的mRNA表达（r=0.821，P<0.05）和IRS-2的mRNA表达（r=0.643，P<0.05）密切相关。
IUGR成年雄性大鼠肝脏中IRS-1和IRS-2表达降低导致IGF-1表达降低，这与生长发育迟缓及胰岛素抵抗有关。IUGR成年雄性大鼠肝脏IR和PI3K的表达与胰岛素抵抗无关。
