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10.2337/db09-1100

http://scihub22266oqcxt.onion/10.2337/db09-1100
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C2844832!2844832!20068131
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suck abstract from ncbi


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pmid20068131      Diabetes 2010 ; 59 (4): 844-9
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  • High Glucose?Induced Oxidative Stress Increases Transient Receptor Potential Channel Expression in Human Monocytes #MMPMID20068131
  • Wuensch T; Thilo F; Krueger K; Scholze A; Ristow M; Tepel M
  • Diabetes 2010[Apr]; 59 (4): 844-9 PMID20068131show ga
  • OBJECTIVE: Transient receptor potential (TRP) channel?induced cation influx activates human monocytes, which play an important role in the pathogenesis of atherosclerosis. In the present study, we investigated the effects of high glucose?induced oxidative stress on TRP channel expression in human monocytes. RESEARCH DESIGN AND METHODS: Human monocytes were exposed to control conditions (5.6 mmol/l d-glucose), high glucose (30 mmol/l d-glucose or l-glucose), 100 ?mol/l peroxynitrite, or high glucose in the presence of the superoxide dismutase mimetic tempol (100 ?mol/l). TRP mRNA and TRP protein expression was measured using quantitative real-time RT-PCR and quantitative in-cell Western assay, respectively. Calcium influx and intracellular reactive oxygen species were measured using fluorescent dyes. RESULTS: Administration of high d-glucose significantly increased reactive oxygen species. High d-glucose or peroxynitrite significantly increased the expression of TRP canonical type 1 (TRPC1), TRPC3, TRPC5, TRPC6, TRP melastatin type 6 (TRPM6), and TRPM7 mRNA and TRPC3 and TRPC6 proteins. High d-glucose plus tempol or high l-glucose did not affect TRP expression. Increased oxidative stress by lipopolysaccharide or tumor necrosis factor-? increased TRP mRNA expression, whereas the reduction of superoxide radicals using diphenylene iodonium significantly reduced TRP mRNA expression. Increased TRPC3 and TRPC6 protein expression was accompanied by increased 1-oleoyl-2-acetyl-sn-glycerol?induced calcium influx, which was blocked by the TRPC inhibitor 2-aminoethoxydiphenylborane. TRPC6 mRNA was significantly higher in monocytes from 18 patients with type 2 diabetes compared with 28 control subjects (P < 0.05). CONCLUSIONS: High d-glucose?induced oxidative stress increases TRP expression and calcium influx in human monocytes, pointing to a novel pathway for increased activation of monocytes and hence atherosclerosis in patients with diabetes.
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