Cadmium induces impaired glucose tolerance in rat by down-regulating GLUT4 expression in adipocytes |
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Authors: | Han Jin C Park Seung Y Hah Byoung G Choi Geum H Kim Yung K Kwon Tae H Kim Eui K Lachaal Moshen Jung Chan Y Lee Wan |
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Institution: | Department of Biochemistry, College of Medicine, Dongguk University, 707 Sukjang-dong, Kyungju, Kyungpook 780-714, South Korea. |
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Abstract: | Cadmium (Cd) has been known to cause hyperglycemia with diabetes-related complications in experimental animals; however, the molecular basis underlying this Cd-induced hyperglycemia is not known. Here, we report the novel finding that the impaired glucose tolerance (IGT) in rats induced by CdCl(2) is accompanied by a drastic (by as much as 90%) and dose-dependent reduction in GLUT4 protein and GLUT4 mRNA levels in adipocytes. The effect was specific to GLUT4; neither GLUT1 nor insulin-responsive aminopeptidase in adipocytes was affected. GLUT2 in hepatocytes was also not affected. Interestingly, the effect on GLUT4 was also specific to adipocytes; the muscle tissues of the Cd-treated rats showed only a slight (<25%) reduction in GLUT4 protein level with no change in GLUT4 message level, and again with no change in GLUT1 protein and its message levels. Although the insulin-induced GLUT4 translocation in adipocytes was not affected by the Cd treatment, the 3-O-methy-D-glucose flux in insulin-stimulated adipocytes of Cd-treated rat was drastically reduced. Together these findings clearly demonstrate that Cd induces IGT in rats by selectively down-regulating GLUT4 expression in adipocytes. |
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Keywords: | Cadmium GLUT4 IGT Hyperglycemia Adipocyte Diabetes |
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