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Similarly, the inositol 1,4,5-trisphosphate-induced store-operated Ca<jats:sup>2+<\/jats:sup>currents were significantly enhanced in the MCs treated with HG for 7 days, and the enhanced response was abolished by both GSK-7975A and La<jats:sup>3+<\/jats:sup>. In contrast, receptor-operated Ca<jats:sup>2+<\/jats:sup>entry in MCs was significantly reduced by HG treatment. Western blotting showed that HG increased the expression levels of STIM1 and Orai1 in cultured MCs. A significant HG effect occurred at a concentration as low as 10 mM, but required a minimum of 7 days. The HG effect in cultured MCs was recapitulated in renal glomeruli\/cortex of both type I and II diabetic rats. Furthermore, quantitative real-time RT-PCR revealed that a 6-day HG treatment significantly increased the mRNA expression level of STIM1. However, the expressions of STIM2 and Orai1 transcripts were not affected by HG. Taken together, these results suggest that HG\/diabetes enhanced SOCE in MCs by increasing STIM1\/Orai1 protein expressions. 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