Environmental Analysis Health and Toxicology

The Korean Society of Environmental Health and Toxicology (환경독성보건학회)
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Effects of Cadmium on Glucose Transport in L6 Myocytes

L6 근육세포에서 포도당 수송능에 미치는 $CdCl_2$의 영향

  • Kang Donghee (College of Pharmacy, Seoul National University) ;
  • Khil Lee-Yong (Lab of Viral and Immunopathogenesis of Diabetes, Julia McFarlane Diabdetes Research Center and Dep. of MID, Faculty of Medicine, University of Calgary) ;
  • park Kwangsik (College of Pharmacy, Dongduk Women's University) ;
  • Lee Byung-Hoon (College of Pharmacy, Seoul National University) ;
  • Moon Chang-Kiu (College of Pharmacy, Seoul National University)
  • Published : 2005.03.01
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Abstract

This study was aimed to know the effect of cadmium chloride (CdCl₂) on glucose transport in L6 myotube and its action mechanism. CdCl₂ increased the 2-deoxy- (l-3H)-D-glucose (2-DOG) uptake 1.9 and 2.4 fold at 10 and 25 μM respectively. To investigate the stimulating-mechanism of glucose transport induced by CdCl₂, the wortmannin and PD98059 were used as PI3K (phosphatidylinositol 3-kinase) inhibitor and MAPK inhibitor respectively, which did not affect 2-DOG uptake. This fact suggests that CdCl₂ induced 2-DOG uptake may not be concerned to the insulin signalling pathway. Whereas nifedipine, a calcium channel blocker, and trifluoperazine, a calmodulin inhibitor, were found to inhibit the 2-DOG uptake stimulted by CdCl₂. In addition, we also measured the ROS (reactive oxygen species) production and GSH level in L6 myotube to investigate the correlation between the glucose uptake and ROS. CdCl₂(25 μM) increased ROS generation approximately 1.5 fold and changed the cellular GSH level, but GSSG/GSH ratio remained unchanged. CdCl₂ stimulated 2-DOG uptake and ROS generation were inhibited by N-acetylcystein. And BSO pretreatment, a potent inhibitor of γ-GCS, resulted in the dramatic decrease of 2-DOG uptake and also the increase of the sensitivity to cadmium cytotoxicity. The obtained results suggest that CdCl₂-stimulated glucose uptake might be based on the activation of HMP shunt as an antioxidant defense mechanism of the cells.

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