Perturbed hepatic phosphoinositol 3-kinase signaling pathway in the rat with intrauterine growth restriction / 中国当代儿科杂志
Chinese Journal of Contemporary Pediatrics
; (12): 221-224, 2009.
Article
ي Zh
| WPRIM
| ID: wpr-347955
المكتبة المسؤولة:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>
النص الكامل:
1
الفهرس:
WPRIM
الموضوع الرئيسي:
Physiology
/
Insulin Resistance
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Signal Transduction
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Rats, Wistar
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Phosphatidylinositol 3-Kinases
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Glycogen Synthase Kinase 3
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Proto-Oncogene Proteins c-akt
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Insulin Receptor Substrate Proteins
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Fetal Growth Retardation
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Glycogen Synthase Kinase 3 beta
المحددات:
Animals
اللغة:
Zh
مجلة:
Chinese Journal of Contemporary Pediatrics
السنة:
2009
نوع:
Article