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• W2036620974 abstract "Rosiglitazone is used to treat Type 2 diabetes because it improves insulin sensitivity. However, the specific molecular mechanism by which this compound acts has not yet been explained.We used fetal rat primary brown adipocytes cultured for 24 h with or without 10 micro mol/l rosiglitazone and further stimulated for 5 min with 10 nmol/l insulin. Next we measured glucose uptake and GLUT4 translocation and submitted the cells to lysis, immunoprecipitation and immunoblotting in order to measure the insulin signalling cascade.Rosiglitazone noticeably activated basal glucose uptake in a manner dependent on p38-mitogen-activated protein kinase. Rosiglitazone also produced a 40% increase in insulin-stimulated glucose uptake as a result of increased GLUT4 translocation to the plasma membrane. This happened without changes in the expression of GLUT4 at the mRNA or protein level. This effect correlated with the potentiation by rosiglitazone of insulin-stimulated Tyr phosphorylation of insulin receptor substrate-1 and to a greater extent of insulin receptor substrate-2. It also correlated with the subsequent activation of phosphatidylinositol 3-kinase and Akt, without changes in protein kinase Czeta activity. Rosiglitazone treatment increased insulin receptor expression and insulin-stimulated Tyr phosphorylation of insulin receptor beta-chain, but decreased insulin-stimulated Ser phosphorylation. It also potentiated insulin-induced Tyr phosphorylation of insulin receptor beta-chain and protein tyrosine phosphatase 1B in co-immunoprecipitates and impaired insulin activation of protein tyrosine phosphatase 1B activity.At the insulin receptor level, rosiglitazone-induced improvements of insulin sensitivity result from two convergent mechanisms: increased insulin receptor expression and insulin receptor activation." @default.
• W2036620974 created "2016-06-24" @default.
• W2036620974 creator A5000786228 @default.
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• W2036620974 date "2003-12-01" @default.
• W2036620974 modified "2023-10-14" @default.
• W2036620974 title "Rosiglitazone produces insulin sensitisation by increasing expression of the insulin receptor and its tyrosine kinase activity in brown adipocytes" @default.
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• W2036620974 doi "https://doi.org/10.1007/s00125-003-1236-z" @default.
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