Effect of proximal tubular glucose transport blockade on urinary enzyme excretions in hyperglycemic rats.
To investigate proximal tubular dysfunction under hyperglycemic status, we infused 10% glucose solution into male Wistar rats with and without 0.16% phloridzin (a specific inhibitor of proximal tubular glucose transportation) and measured the urinary excretion rates of enzymes that are derived predominantly from proximal tubules. We used 10% mannitol solution and 0.9% saline as controls. Urinary excretion levels of N-acetyl-ss-D-glucosaminidase, alanine aminopeptidase, gamma-glutamyl transpeptidase and dipeptidyl aminopeptidase IV were significantly increased in the 10% glucose-loaded group. In contrast, these increased enzyme excretions were not observed in the 10% mannitol or 0.9% saline-loaded group. Moreover, addition of 0.16% phloridzin to 10% glucose solution completely prevented these increases in N-acetyl-beta-D-glucosaminidase, alanine aminopeptidase and gamma-glutamyl transpeptidase excretion, and slightly decreased dipeptidyl aminopeptidase IV excretion. At the end of the infusion study, a rise in renal cortical sorbitol concentration of the 10% glucose-loaded group was about 2 times higher than the 0.9% saline or 10% mannitol-loaded group. However, in the group that received both glucose and phloridzin, elevation of renal cortical sorbitol concentration was not observed. This study showed that glucose-load results in both abnormal enzymuria and renal cortical sorbitol accumulation; they were completely prevented by phloridzin.
Ishii
N
N
Department of Clinical Chemistry, Kitasato University School of Allied Health Sciences, Kanagawa, Japan.
Ogawa
Z
Z
Itoh
H
H
Ikenaga
H
H
Saruta
T
T
D000118:Acetylglucosaminidase / Q000652:urine*; D000410:Alanine Transaminase / Q000652:urine*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000652:urine*; D005919:Glomerular Filtration Rate; D005947:Glucose / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D006943:Hyperglycemia / Q000201:enzymology / Q000503:physiopathology* / Q000652:urine; D007668:Kidney / Q000737:chemistry; D007672:Kidney Cortex / Q000737:chemistry; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008353:Mannitol / Q000378:metabolism / Q000494:pharmacology; D010695:Phlorhizin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013012:Sorbitol / Q000032:analysis; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000652:urine*
D001786:Blood Glucose; D008353:Mannitol; D013012:Sorbitol; D010695:Phlorhizin; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D000118:Acetylglucosaminidase; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D005947:Glucose