title: High glucose inhibits glucose uptake in renal proximal tubule cells by oxidative stress and protein kinase C.
abstract: BACKGROUND
  High 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 alpha-methyl-D-glucopyranoside (alpha-MG) uptake in primary cultured rabbit renal proximal tubule cells (PTCs).
  
  
  METHODS
  PTCs were incubated with 25 mmol/L glucose alone or combined with taurine, ascorbic acid, catalase, staurosporine, and bisindolylmaleimide I. Then alpha-MG uptake and lipid peroxide (LPO) formation were examined.
  
  
  RESULTS
  Twenty-five mmol/L glucose from four hours, but not 25 mmol/L mannitol, inhibited alpha-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 alpha-MG uptake, 25 mmol/L glucose significantly increased LPO by 27% compared with control. However, 10 mmol/L glucose did not affect alpha-MG uptake and LPO formation. Taurine (2 mmol/L), ascorbic acid (1 mmol/L), endogenous antioxidants, or catalase (600 U/mL) significantly blocked 25 mmol/L glucose-induced increase of LPO formation and inhibition of alpha-MG uptake. In the experiment to examine the effects of protein kinase C on LPO formation, 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 ng/mL) increased LPO formation, and staurosporine (10(-7) mol/L) and bisindolylmaleimide I (10(-6) mol/L) totally blocked 25 mmol/L glucose-induced increase of LPO formation and inhibition of alpha-MG uptake. In addition, taurine reduced TPA-induced increase of LPO formation and inhibition of alpha-MG uptake.
  
  
  CONCLUSIONS
  High glucose induces, in part, the inhibition of alpha-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.
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Kwangju, Korea. hjhan@chonnam.chonnam.ac.kr
authors.forename: H J
authors.initials: HJ
authors.lastname: Han
authors.forename: H J
authors.initials: HJ
authors.lastname: Choi
authors.forename: S H
authors.initials: SH
authors.lastname: Park
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000502:physiology; D005947:Glucose / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D008054:Lipid Peroxides / Q000096:biosynthesis; D008757:Methylglucosides / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D018384:Oxidative Stress / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D011817:Rabbits
chemical_list: D008054:Lipid Peroxides; D008757:Methylglucosides; C027020:methylglucoside; D011493:Protein Kinase C; D005947:Glucose