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Perturbed hepatic phosphoinositol 3-kinase signaling pathway in the rat with intrauterine growth restriction
LIU Xiao-Mei, JIAO Yi-Sheng, PAN Li-Li, LU Yan, LI Shu-Qin
Chinese Journal of Contemporary Pediatrics ›› 2009, Vol. 11 ›› Issue (03) : 221-224.
PDF(1137 KB)
PDF(1137 KB)
Perturbed hepatic phosphoinositol 3-kinase signaling pathway in the rat with intrauterine growth restriction
OBJECTIVE: To determine the molecular mechanisms linking intrauterine growth restriction (IUGR) to adult type 2 diabetes mellitus, the effect of IUGR on the hepatic post-receptor insulin-signaling pathway was investigated in the adult offspring. METHODS: The IUGR model was prepared by maternal protein-malnutrition. Western blotting analysis was undertaken to assess hepatic expression of insulin receptor substrate (IRS-2), phosphoinositol 3-kinase (PI-3K), protein kinase B (PKB), phosphorylated PKB-Ser473 and glycogen synthase kinase (GSK) 3 in 8-week-old male IUGR rats. RESULTS: The basal levels of PI-3K protein decreased in IUGR rats compared with normal controls (P<0.01), whereas GSK-3β protein level significantly increased in IUGR rats (P<0.01). Both PKB and phosphorylated PKB-Ser473 protein levels significantly decreased in the liver of IUGR rats compared with normal controls (P<0.01). After insulin administration, phosphorylated PKB-Ser473 significantly increased to 182% of basal level in control rats (P<0.01); However, phosphorylation of PKB which responded to insulin was markedly blunted in IUGR rats compared with controls and only increased to 123% of basal level (P<0.05). ConclusionsThe level of PI-3K and PKB and phosphorylated PKB-Ser473 expression decreased in the liver of IUGR rats, whereas the levels of GSK-3β protein increased. It may contribute to the pathogenesis of insulin resistance in the IUGR rats.［Chin J Contemp Pediatr, 2009, 11 (3):221-224］
Intrauterine growth restriction / Insulin resistance / Signal transduction / Phosphoinositol 3-kinase / Rats
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