Reduction of the PI3K/Akt related signaling activities in skeletal muscle tissues involves insulin resistance in intrauterine growth restriction rats with catch-up growth

Abstract

Individuals with intrauterine growth retardation (IUGR) are prone to insulin resistance, whereas the underlying molecular mechanisms remain unclear. In this study, we investigated if the PI3K/Akt signaling pathway in skeletal muscle tissues involves insulin resistance in IUGR offsprings, particularly ones with catch-up growth. An IUGR rat model was established by feeding rats an isocaloric (30.50 Kcal/g) diet containing 8% protein (low-protein diet) from day 1 of pregnancy until the birth of their pups. Glucometabolic parameters were measured and compared. Quantitative PCR and western blot were performed to assess mRNA and protein expression changes of the PI3K/Akt related signals in skeletal muscle tissues. Pearson analysis was used to assess the correlation of the PI3K/Akt signaling level and catch-up growth with the insulin resistance index (IRI). The values of fasting plasma glucose, fasting insulin and IRI were significantly higher, whereas insulin sensitivity index was significantly lower in IUGR offsprings than those in the controls. The PI3K mRNA and protein levels as well as the phospho-AktSer473 levels were significantly lower in IUGR offsprings compared to the controls. Reductions of GLUT4 as well as increases of PTEN and nuclear fractional PPARγ were detected in IUGR offsprings. Catch-up growth IUGR rats were positively correlated with insulin resistance and underwent more remarkable alterations of the PI3K, PTEN and GLUT4 expressions. Our results demonstrated that rats born IUGR developed insulin resistance later in life, which was likely mediated by reductions of the PI3K/Akt related signaling activities, particularly in those with excess catch-up growth.