Glucagon과 insulin이 glutathione 항상성에 미치는 영향: 세포신호전달체계 및 glutathione transport system의 역할

Effects of Glucagon and Insulin on Glutathione Homeostasis: Role of Cellular Signaling Pathways and Glutathione Transport System

  • 김봉희 (충남대학교 약학대학, 충남대학교 형질전환 복제돼지 센터) ;
  • 오정민 (충남대학교 약학대학, 충남대학교 형질전환 복제돼지 센터) ;
  • 윤강욱 (충남대학교 약학대학, 충남대학교 형질전환 복제돼지 센터) ;
  • 김충현 (충남대학교 약학대학, 충남대학교 형질전환 복제돼지 센터) ;
  • 김상겸 (충남대학교 약학대학, 충남대학교 형질전환 복제돼지 센터)
  • Kim, Bong-Hee (College of Pharmacy and Research Center for Transgenic Cloned Pigs, Chungnam National University) ;
  • Oh, Jung-Min (College of Pharmacy and Research Center for Transgenic Cloned Pigs, Chungnam National University) ;
  • Yun, Kang-Uk (College of Pharmacy and Research Center for Transgenic Cloned Pigs, Chungnam National University) ;
  • Kim, Chung-Hyeon (College of Pharmacy and Research Center for Transgenic Cloned Pigs, Chungnam National University) ;
  • Kim, Sang-Kyum (College of Pharmacy and Research Center for Transgenic Cloned Pigs, Chungnam National University)
  • 발행 : 2007.09.30

초록

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 efflux in response to glucagon and insulin were examined in primary cultured rat hepatocytes. The GSH concentrations 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. Pretreatment 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.

키워드

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