Augmented arginine uptake, through modulation of cationic amino acid transporter-1, increases GFR in diabetic rats.
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.
Schwartz
Idit F
IF
Nephrology Department, Tel Aviv Sourasky Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel. nmdri@netvision.net.il
Iaina
Adrian
A
Benedict
Yishayahu
Y
Wollman
Yoram
Y
Chernichovski
Tamara
T
Brasowski
Eli
E
Misonzhnik
Faina
F
Ben-Dor
Amir
A
Blum
Miriam
M
Levo
Yoram
Y
Schwartz
Doron
D
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
D027201:Cationic Amino Acid Transporter 1; D027202:Cationic Amino Acid Transporter 2; D007527:Isoenzymes; D012333:RNA, Messenger; D001120:Arginine; D001119:Arginase