High glucose inhibits glucose uptake in renal proximal tubule cells by oxidative stress and protein kinase C

High glucose inhibits glucose uptake in renal proximal tubule cells by oxidative stress and protein kinase C.BackgroundHigh glucose has been considered to play an important role in alteration of renal proximal tubule transporter's activity. This study examined the mechanism by which high glucose modulates α-methyl-d-glucopyranoside (α-MG) uptake in primary cultured rabbit renal proximal tubule cells (PTCs).MethodsPTCs were incubated with 25 mmol/L glucose alone or combined with taurine, ascorbic acid, catalase, staurosporine, and bisindolylmaleimide I. Then α-MG uptake and lipid peroxide (LPO) formation were examined.ResultsTwenty-five mmol/L glucose from four hours, but not 25 mmol/L mannitol, inhibited α-MG uptake by 23% compared with 5 mmol/L glucose (control). In the study to examine the relationship of oxidative stress in the high-glucose–induced inhibition of α-MG uptake, 25 mmol/L glucose significantly increased LPO by 27% compared with control. However, 10 mmol/L glucose did not affect α-MG uptake and LPO formation. Taurine (2 mmol/L), ascorbic acid (1 mmol/L), endoge-nous antioxidants, or catalase (600 U/mL) significantly blocked 25 mmol/L glucose-induced increase of LPO formation and inhibition of α-MG uptake. In the experiment to examine the effects of protein kinase C on LPO formation, 12-O-tetradeca-noylphorbol-13-acetate (TPA; 100 ng/mL) increased LPO formation, and staurosporine (10-7 mol/L) and bisindolylmalei-mide I (10-6 mol/L) totally blocked 25 mmol/L glucose-induced increase of LPO formation and inhibition of α-MG uptake. In addition, taurine reduced TPA-induced increase of LPO formation and inhibition of a-MG uptake.ConclusionHigh glucose induces, in part, the inhibition of α-MG uptake through LPO formation, and activation of protein kinase C may play a role in high-glucose–induced LPO formation in the primary cultured rabbit renal PTCs