title: Effect of paraquat-induced oxidative stress on insulin regulation of insulin-like growth factor-binding protein-1 gene expression.
abstract: 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.
authors.affiliation: Department of Agricultural Chemistry, Faculty of Agriculture, Meiji University, Kawasaki, Kanagawa 214-8571, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Kimura
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Katsumata
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ozawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tawara
authors.forename: Kiharu
authors.initials: K
authors.lastname: Igarashi
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Cho
authors.forename: Norihiro
authors.initials: N
authors.lastname: Shibata
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Hakuno
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Takahashi
authors.forename: Asako
authors.initials: A
authors.lastname: Takenaka