Molecular analysis of glucose transporter in glomerular mesangial cells

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It has been known that the abnormalities of mesangial area in glomeruli play a crucial role in the progression of diabetic nephropathy, and the mesangial cells might participate in the evolution of these abnormalities. In order to clarify the role of mesangial cells, the cells were investigated under high concentration of glucose in vitro and various metabolic derangements have been detected, which might be related to the mesangial abnormalities seen in vivo. The glucose appears to cause various.metabolic abnormalities in mesangial cells after transported intracellularly via specific glucose transporter(GLUT). In this study, the glucose transporter in mesangial cells was characterized by western blot and northern blot analyses. The western blotting using monoclonal antibodies against GLUTs 1 and 4 showed the presence of GLUT 1 but failed to detect GLUT 4. The northern blot analysis using cDNAs for GLUT 1,2,3,4,and 5 revealed the presence of GLUT 1 mRNA only, which was compatible with the results of western blotting. Furthermore, insulin-like growth factor 1 (IGF-1), which was able to increase the glucose uptake in mesangial cells, was found to stimulate the gene expression of GLUT 1. Since the mesangial cells possesses an abundant amount of receptors for IGF-1 and the IGF-1 levels in renal tissue is increased in diabetic state, the amount of glucose transport in mesangial cells may be regulated by IGF-1 and be increased in diabetes mellitus. In summary, GLUT 1 is a main glucose transporter in mesangial cells, regulated by IGF-1, and may play a role in the evolution of metabolic derangements found in diabetes mellitus.