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Journal of Environmental Toxicology 2007;22(3):227-233.
세포신호전달체계 및 glutathione transport system의 역할
김봉희, 오정민, 윤강욱, 김충현, 김상겸
Effects of Glucagon and Insulin on Glutathione Homeostasis: Role of Cellular Signaling Pathways and Glutathione Transport System
Bong-Hee Kim , Jung Min Oh , Kang Uk Yun , Chung Hyeon Kim , Sang Kyum Kim
ABSTRACT
  It has been reported that hepatic glutathione (GSH) levels are decreased in diabetic patients, and glucagon increases hepatic efflux of GSH into blood. The signaling pathways responsible for mediating the glucagon effects on GSH efflux, however, are unknown. The signaling pathways involved in the regulation of GSH ef-flux in response to glucagon and insulin were examined in primary cultured rat hepatocytes. The GSH concen-trations in the culture medium were markedly increased by the addition of glucagon, although cellular GSH levels are significantly decreased by glucagon. Insulin was also increased the GSH concentrations in the culture medium, but which is reflected in elevations of both cellular GSH and protein. Treatment of cells with 8-bromo -cAMP or dibutyryl-cAMP also resulted in elevation of the GSH concentrations in the culture medium. Pre-treatment with H89, a selective inhibitor of protein kinase A, before glucagon addition markedly attenuated the glucagon effect. These results suggest that glucagon changes GSH homeostasis via elevation of GSH efflux, which may be responsible for decrease in hepatic GSH levels observed in diabetic condition. Furthermore, the present study implicates cAMP and protein kinase A in mediating the effect of glucagon on GSH efflux in primary cultured rat hepatocytes.
Keywords: glutathione; glucagon; insulin; hepatic efflux; cellular signaling
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