title: Augmented arginine uptake, through modulation of cationic amino acid transporter-1, increases GFR in diabetic rats.
abstract: BACKGROUND
  It is suggested that either arginine or its metabolites, nitric oxide and polyamines play a role in the renal hemodynamic alterations observed in the early stages of diabetes. Yet, the regulation of arginine transport in diabetic kidneys has never been studied.
  
  
  METHODS
  Arginine uptake was determined in glomeruli harvested from control rats; diabetic rats (2 weeks following an intraperitoneal injection of streptozotocin, 60 mg/kg body weight); rats, 4 days following left nephrectomy (a nondiabetic model of hyperfiltration); diabetes + lysine (0.5% in the drinking water to attenuate arginine uptake); and control + lysine.
  
  
  RESULTS
  Glomerular arginine transport was significantly increased in diabetic rats, but remained unchanged following uninephrectomy. Lysine abolished the increase in arginine uptake in diabetic rats but had no effect in controls. The increase in creatinine clearance observed in diabetes was completely abolished by lysine. Using reverse transcription-polymerase chain reaction (RT-PCR), Northern blotting, and immunohistochemistry, we found a significant increase in glomerular cationic amino acid transporter-1 (CAT-1) expression in diabetic animals, which was unaffected by lysine. When human endothelial cells were incubated with arginine end products no effect on arginine transport was observed. However, only in the presence of 0.5 mM/L sodium nitroprusside (SNP) an augmented steady-state CAT-1 mRNA was demonstrated by RT-PCR.
  
  
  CONCLUSIONS
  In a rat model of early diabetes, glomerular arginine uptake is elevated through modulation of CAT-1 expression, thus, contributing to the pathogenesis of hyperfiltration. Increased nitric oxide formation may play a role in this process.
authors.affiliation: Nephrology Department, Tel Aviv Sourasky Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel. nmdri@netvision.net.il
authors.forename: Idit F
authors.initials: IF
authors.lastname: Schwartz
authors.forename: Adrian
authors.initials: A
authors.lastname: Iaina
authors.forename: Yishayahu
authors.initials: Y
authors.lastname: Benedict
authors.forename: Yoram
authors.initials: Y
authors.lastname: Wollman
authors.forename: Tamara
authors.initials: T
authors.lastname: Chernichovski
authors.forename: Eli
authors.initials: E
authors.lastname: Brasowski
authors.forename: Faina
authors.initials: F
authors.lastname: Misonzhnik
authors.forename: Amir
authors.initials: A
authors.lastname: Ben-Dor
authors.forename: Miriam
authors.initials: M
authors.lastname: Blum
authors.forename: Yoram
authors.initials: Y
authors.lastname: Levo
authors.forename: Doron
authors.initials: D
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics; D001120:Arginine / Q000378:metabolism*; D001692:Biological Transport; D027201:Cationic Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism*; D027202:Cationic Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D005786:Gene Expression Regulation; D005919:Glomerular Filtration Rate; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000235:genetics; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D027201:Cationic Amino Acid Transporter 1; D027202:Cationic Amino Acid Transporter 2; D007527:Isoenzymes; D012333:RNA, Messenger; D001120:Arginine; D001119:Arginase