title: Decreased expression of glucose and peptide transporters in rat remnant kidney.
abstract: The loss of renal mass induces tubular hypertrophy as well as glomerular sclerosis and results in the end stage of renal disease. However, there is little information about adaptation of tubular glucose and peptide reabsorption under conditions of chronic renal failure. In the present study, we performed functional and molecular analyses focused on the tubular reabsorption of filtered glucose and small peptides using 5/6 nephrectomized rats at 16 weeks, as a model of chronic renal failure. Sixteen weeks after 5/6 nephrectomy or sham treatment, the brush-border membranes and total RNA were obtained from the renal cortex to evaluate the uptake of Na(+) gradient-dependent D-glucose and H(+) gradient-dependent glycylsarcosine. The amounts of SGLT and PEPT mRNA levels were quantified by competitive PCR. The urinary glucose/creatinine ratio was markedly higher in nephrectomized rats than in sham-operated controls. Na(+)-dependent glucose uptake by the isolated renal brush-border membrane vesicles was markedly decreased in nephrectomized rats compared with that in sham-operated controls. However, H(+)-dependent peptide transport, another secondary active transport system in the brush-border membranes, was maintained. In addition, kinetic analysis revealed that both SGLT1 (high-affinity type)- and SGLT2 (low-affinity type)-mediated Na(+)/glucose uptake had markedly decreased Vmax values, but not Km values. Furthermore, competitive PCR demonstrated that the mRNA expression levels of SGLT2, PEPT1 and PEPT2, but not SGLT1, were markedly depressed. These findings suggested that loss of SGLT2 during chronic renal failure implies a high risk of renal glucosuria.
authors.affiliation: Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Nakamura
authors.forename: Satohiro
authors.initials: S
authors.lastname: Masuda
authors.forename: Kazushige
authors.initials: K
authors.lastname: Takahashi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saito
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okuda
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Inui
mesh_terms: D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis; D009392:Nephrectomy; D000074011:Peptide Transporter 1; D010455:Peptides / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D051269:Sodium-Glucose Transporter 1; D051297:Sodium-Glucose Transporter 2; D027981:Symporters / Q000096:biosynthesis
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D000074011:Peptide Transporter 1; D010455:Peptides; D012333:RNA, Messenger; C082186:SLC15A1 protein, human; C489940:Slc15a1 protein, rat; C495676:Slc5a1 protein, rat; C490300:Slc5a2 protein, rat; D051269:Sodium-Glucose Transporter 1; D051297:Sodium-Glucose Transporter 2; D027981:Symporters; C093694:hydrogen-coupled oligopeptide transporter PepT2; D005947:Glucose