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

The differential role of L-selectin and ICAM-1 in Th1-type and Th2-type contact hypersensitivity.

Sensitization and challenge using DNFB induce contact hypersensitivity (CHS) with predominant type 1 helper (Th1) cell infiltration, whereas those using FITC generate CHS with Th2 cell infiltration. CHS results from inflammatory cell infiltration, a process that is highly regulated by the expression of multiple adhesion molecules. We attempted to determine the role of L-selectin and ICAM-1 in Th1- and Th2-type CHS induced by DNFB or FITC in mice lacking either L-selectin, ICAM-1, or both. Th1-type CHS induced by DNFB was inhibited by L-selectin and/or ICAM-1 deficiency, which was associated with reduced IFN-gamma expression. Similarly, Th2-type CHS induced by FITC was inhibited by L-selectin deficiency. However, Th2-type CHS was increased by ICAM-1 deficiency and accompanied by increased Th2 cytokine expression. Infiltration of in vitro-generated Th1 cells into the FITC-challenged skin decreased in ICAM-1-deficient mice, whereas in vitro-generated Th2 cell infiltration increased, suggesting that ICAM-1 mediates Th1 cell migration and that in the absence of ICAM-1, Th1 cell recruitment decreased, whereas relative Th2 cell migration increased. These results suggest that ICAM-1 mediates Th1 cell recruitment irrespective of DNFB or FITC and that L-selectin recruits Th1 cells in Th1-type CHS, whereas it recruits Th2 cells in Th2-type CHS

Transportation Investments and Productivity Analysis of a Japanese Case Study

Over the last two decades, there have been several studies on productivity related to transportation investments in not only Japan but also several foreign countries. However, these prior studies did not achieve common results as they did not use a unified format for measuring the service level of the transportation network and using the dataset. Therefore, this study classifies previous studies from six points of view. These are analytical method, functional type, explained variable, service level of the transportation network, aggregation level, and estimation method. This study examines the differences in results caused by the diversity of analytical methods. In addition, this study estimates the production function using two analytical methods with Japanese data. Then, the relationship between the productivity and transport investments is revealed. From this result, several issues are confirmed

Dietary protein restriction increases hepatic leptin receptor mRNA and plasma soluble leptin receptor in male rodents.

Leptin is an adipokine that regulates adipose tissue mass through membrane-anchored leptin receptor (Ob-R). Extracellular domain of Ob-R in plasma is called soluble leptin receptor (sOb-R), and is the main leptin-binding protein. Based on a previous DNA microarray analysis that showed induction of hepatic Ob-R mRNA in low-protein diet-fed mice, this study aimed to clarify the effect of dietary protein restriction on hepatic Ob-R mRNA and plasma sOb-R levels. First, the effect of protein restriction on hepatic Ob-R mRNA level was examined together with fasting and food restriction using male rats as common experimental model for nutritional research. Hepatic Ob-R mRNA level was increased by feeding low-protein diet for 7 d, although not significantly influenced by 12-h fasting and sixty percent restriction in food consumption. Then, effect of protein restriction on liver Ob-R and plasma sOb-R was investigated using male mice because specific sOb-R ELISA was more available for mice. Hepatic Ob-R mRNA level was also increased in protein restricted-mice although it did not increase in hypothalamus. Hepatic Ob-R protein was decreased, whereas plasma sOb-R was increased by protein restriction. Because the concentration of sOb-R increased without changing plasma leptin concentration, free leptin in plasma was significantly reduced. The direct effect of amino acid deprivation on Ob-R mRNA level was not observed in rat hepatoma cells H4IIE cultured in amino acid deprived medium. In conclusion, dietary protein restriction increased hepatic Ob-R mRNA, resulting in increased plasma sOb-R concentration, which in turn, reduces plasma free leptin level and may modulate leptin activity