Effect of paraquat-induced oxidative stress on insulin regulation of insulin-like growth factor-binding protein-1 gene expression.
Oxidative stress is thought to play a role in the development of insulin resistance. In order to elucidate the molecular effect of oxidative stress on liver insulin signaling, we analyzed the effect of paraquat (1,1-dimethyl-4,4-dipyridynium; PQ)-derived oxidative stress on the expression of insulin-dependent genes and activation of liver insulin signaling pathway. Incubation of primary cultured rat hepatocytes with 2 mM PQ for 6 h impaired the suppressive effect of insulin on insulin-like growth factor-binding protein-1 (IGFBP-1) gene expression, but did not influence glucose-6-phosphatase gene expression. Insulin-dependent phosphorylation or activation of insulin receptor, insulin receptor substrate-1 and -2, phosphatidylinositol 3-kinase, Akt and forkhead in rhabdomyosarcoma were not affected by PQ pre-treatment. In contrast, PQ treatment impaired insulin-dependent phosphorylation of mammalian target of rapamycin (mTOR). These results indicate that PQ-induced oxidative stress impairs insulin-dependent mTOR activation and that this impairment probably causes inhibition of insulin-dependent repression of IGFBP-1 expression.
Kimura
Kumi
K
Department of Agricultural Chemistry, Faculty of Agriculture, Meiji University, Kawasaki, Kanagawa 214-8571, Japan.
Katsumata
Yoshihito
Y
Ozawa
Takahiro
T
Tawara
Satoshi
S
Igarashi
Kiharu
K
Cho
Yoshitake
Y
Shibata
Norihiro
N
Hakuno
Fumihiko
F
Takahashi
Shin-Ichiro
S
Takenaka
Asako
A