[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-3beta 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).


CONCLUSIONS
The level of PI-3K and PKB and phosphorylated PKB-Ser473 expression decreased in the liver of IUGR rats, whereas the levels of GSK-3beta protein increased. It may contribute to the pathogenesis of insulin resistance in the IUGR rats.
Liu
Xiao-Mei
XM
Experiment Research Center, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Jiao
Yi-Sheng
YS
Pan
Li-Li
LL
Lu
Yan
Y
Li
Shu-Qin
SQ
D000818:Animals; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000032:analysis; D000071679:Glycogen Synthase Kinase 3 beta; D055504:Insulin Receptor Substrate Proteins / Q000032:analysis; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000032:analysis / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*
D055504:Insulin Receptor Substrate Proteins; C526299:Irs2 protein, rat; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3