Inhibition of p53 Relieves Insulin Resistance in Fetal Growth Restriction Mice with Catch-Up Growth via Activating IGFBP3/IGF-1/IRS-1/Akt Signaling Pathway.

To investigate insulin resistance of the fetal growth restriction (FGR) mice with catch-up growth (CUG) and the underlying mechanism, in this study, low protein diet was used during pregnancy to establish the FGR mice model, and high fat diet was applied to establish the CUG model of FGR mice. The insulin and Pifithrin-α stimulation was performed via intraperitoneal injection. The physical characters, biochemical parameters, expression of related molecules in each group were detected via ELISA, RT-PCR, WB, etc. The results showed FBG, FINS and HOAM-IR in CUG-FGR group were higher than those in high fat feeding control group (NC+HF), but the content of IGF-1 in blood was lower than that in NC + HF group. Meanwhile, RT-PCR and WB showed that the expression of IGF was negatively correlated with the expression of P53/IGFBP3. Moreover, the expression of P-IRS/p-PI3K/p-Akt decreased with the increasing of HOAM-IR in IGF signaling pathway. When the mice were injected with Pifithrin-α, the phosphorylation level of IGF signaling pathway and insulin resistance index in the CUG-FGR group were increased and decreased, respectively. In conclusion, insulin resistance in CUG-FGR mice is correlated with the IGFBP3/IGF-1/IRS-1/Akt signaling pathway and inhibited p53 could activate this signaling pathway and relieve insulin resistance.