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Effects of Cadmium on Glucose Transport in L6 Myocytes  

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)
Publication Information
Environmental Analysis Health and Toxicology / v.20, no.1, 2005 , pp. 75-85 More about this Journal
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.
Keywords
Cadmium; Glucose transport; Myocytes; ROS; GHS;
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