Regulation of Glucose Uptake in Mesangial Cells Stimulated by High Glucose: Role of Angiotensin II and Insulin

Mesangial cells (MCs) play a central role in the pathogenesis of diabetic nephropathy (DN). MC dysfunction arises from excessive glucose uptake through insulin-independent glucose transporter (GLUT1). the role of the insulin-dependent transporter (GLUT4) remains unknown. This study evaluated the effect of high glucose on GLUT1, GLUT4, and fibronectin expression levels. Glucose uptake was determined in the absence and presence of insulin. Angiotensin 11 has been implicated as a mediator of MC abnormalities in DN, and its effects on the GLUTs expression were evaluated in the presence of losartan. MCs were exposed to normal (NG, 10 mM) or high (HG, 30 mM) glucose for 1, 4,12, 24 and 72 hrs. Glucose uptake was elevated from 1 hr up to 24 hrs of HG, but returned to NG levels after 72 hrs. HG induced an early (1-, 4-, and 12-hrs) rise in GLUT1 expression, returning to NG levels after 72 hrs, whereas GLUT4 was overexpressed at later timepoints (24 and 72 hrs). HG during 4 hrs induced a 40% rise in glucose uptake, which was unaffected by insulin. in contrast, after 72 hrs, glucose uptake was increased by 5006, only under insulin stimulus. Losartan blunted the effects of HG on GLUT1, GLUT4, and fibronectin expression and on glucose uptake. Results suggest that MCs can be highly susceptible to the HG environment since they uptake glucose in both an insulin-independent and insulin-dependent manner. the beneficial effects of angiotensin 11 inhibition in DN may also involve a decrease in the rate of glucose uptake by MCs. Exp Biol Med 234:1095-1101, 2009Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundacao Oswaldo Ramos (FOR)Fundo de Auxilio aos Docentes e Alunos da UNIFESP (FADA)Universidade Federal de São Paulo, Div Renal, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Div Renal, BR-04023900 São Paulo, BrazilWeb of Scienc