IRS Expression Levels In Livers And Muscles Of Intrauterine Growth Retarded Rats And Metabolic Syndrome

Objective In the past decade, several epidemiological studies have shown a relationship between intrauterine growth retardation(IUGR)and insulin resistance, type 2 diabetes and cardiovascular disease in adulthood. We developed an IUGR model of Sprague-Dawley rats and investigated insulin receptor substrate-1(IRS-1) and insulin receptor substrate-2 (IRS-2) expression levels in liver tissues and muscles of the IUGR rats.Methods An IUGR animal model was established by maternal nutrition restriction during pregnancy. 8 newborn IUGR pups and 8 normal newborn control pups randomly selected were executed immediately after birth with liver tissues, cardiac muscles and quadriceps femoris extracted. The remains were divided equally and fed by normal mother milk for 3 weeks respectively. 8 IUGR pups (male 4, female 4) and 8 control pups (male 4, female 4) randomly selected were executed with liver tissues and quadriceps femoris extracted and plasma samples were collected for testing of fasting plasma glucose and insulin. HOMA-IR indexes of IUGR group and normal control group were calculated. Total RNA of liver tissues and quadriceps femoris was extracted using TRIZOL Reagent. The mRNA expression levels of IRS-1, IRS-2 were detected by RT-PCR. Immunohistochemical stainings were used to analyse IRS-1, IRS-2 proteins.Results Body weight, body length of IUGR rats were significantly lower than normal control rats at the same age. IRS-1, IRS-2 mRNA relative expression levels in liver tissues of newborn IUGR rats were significantly lower than that of control group respectively. IRS-1 mRNA relative expression level in cardiac muscle of newborn IUGR rats was significantly higher than that in newborn control rats. IRS-1 mRNA relative expression level in quadriceps femoris and IRS-2 mRNA in cardiac muscle of newborn IUGR rats were significantly lower than those in newborn control rats, respectively. IRS-2 mRNA relative expression level in quadriceps femoris had no significant difference with that in newborn control rats.IRS-1 mRNA relative expression levels in quadriceps femoris and IRS-2 mRNA relative expression levels in liver tissues of IUGR rats at wk 4 were significantly lower than that of control group at wk 4 respectively, while IRS-1 mRNA relative expression levels in liver tissues and IRS-2 mRNA relative expression levels in quadriceps femoris had no significant difference between the two groups. Fasting plasma insulin and HOMA-IR of IUGR rats at wk 4 were higher than that of control group at wk 4. The results of immunohistochemical stainings were consistent with those of RT-PCR.Conclusions Tissue-specific gene expression of IRS-1 was found in IUGR group. Up-regulation of IRS-1 gene expression in cardiac muscle of IUGR group was the result of adaptation to maternal undernutrition. IRS-2 expression levels in liver tissues and IRS-1 expression levels in skeletal muscle of IUGR rats at wk 0, 4 were significantly lower than that of normal rats at the same age, and induced insulin resistance, which might be one of the molecular mechanisms of IUGR having increased risks of metabolic syndrome.