Time Sequence Expressions Of Insulin Receptor Substrates In Adipocytes Of Newborn Rats With Intrauterine Growth Retardation

Objective To investigate the time sequence expressions of insulin receptor substrate- 1 (IRS-1) and insulin receptor substrate-2 (IRS-2) in adipocytes of newborn rats with intrauterine growth restricttion (IUGR), in order to explore the effect on the insulin resistance in adult rats with IUGR.Methods Sprague-Dawley (SD) rats (clean grade) were randomly divided into control group and food-restricted group after fertilization. Food-restricted group were received about 30% food of control group every day through the whole pregnant period to establish IUGR animal model, and were fed with increased breast milk from postnatal day 1 to 21 to establish IUGR animal model with catch-up growth (IUGR-CG). Fasting serous glucose, insulin and triglyceride were measured by taking blood from heart ventricles of 4-week old SD rats to get insulin resistance index (IRI). Preadipocytes and mature adipocytes, which were obtained from distal epididymis, around kidney, groin of different aged SD rats(1-week, 3-week, 5-week and 7-week old), were primary cultured, and the former were induced to differentiate toward mature adipocytes. The mature adipocytes and differentiated preadipocytes were identified with oil red O staining. The levels of IRS-1, IRS-2 in the two kinds of mature adipocytes were detected by Real-time PCR and Western blot.Results Birth weight, nose-rump length and body mass index(BMI) of IUGR newborn rats were significantly less than the control (p<0.01), however, birth weight and BMI grew faster than those in the control group (p<0.01). The levels of fasting serous glucose, insulin, IRI and triglyceride of IUGR-CG rats were higher than those in the control group at 4-week old (p<0.01). The relative expression levels of IRS-1, IRS-2 mRNA in primary cultured mature adipocytes were significantly lower than those in the control group at 5-week and 7-week old (p=0.014, 0.047), the relative expression levels of IRS-1, IRS-2 mRNA in mature adipocytes differentiated from preadipocytes were significantly lower than those in the control group at 5-week and 7-week old (p=0.030, 0.039). The relative expression levels of IRS-1, IRS-2 protein in two kinds of mature adipocytes were significantly lower than those in the control group from postnatal week 1 to 7 ( p<0.05).Conclusion IRS-1 and IRS-2 expression levels are downregulated in adipocytes of IUGR rats with catch-up growth at different age, may contribute to disfunction of adipocytes, which maybe play an important role in insulin resistance in IUGR rats with catch-up growth.