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Lack of SGLT1 enhances renal oxidative stress, reduces kidney weight, and blunts diabetic glomerular hyperfiltration
Author(s) -
Vallon Volker,
Gerasimova Maria,
Satriano Joe,
Gorboulev Valentin,
Cunard Robyn,
Koepsell Hermann,
Rieg Timo
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1038.2
Subject(s) - medicine , endocrinology , diabetes mellitus , creatinine , renal function , albuminuria , oxidative stress , renal glucose reabsorption , kidney , streptozotocin , type 2 diabetes
To gain insights on the role of the Na‐glucose cotransporter SGLT1 in the kidney, knockout mice were generated. All mice received a low glucose diet to prevent malabsorption. Sglt1−/− mice have similar blood glucose levels as wild‐type (WT) but enhanced glucosuria and fractional renal excretion of glucose (3.1±0.3 vs 0.2±0.1%; n=6–7; P<0.001). Sglt1−/− have greater urinary H2O2 (177±18 vs 129±9nmol/mg creatinine; P<0.01) and smaller kidneys vs WT (10.9±0.3 vs 13.5±0.5mg/g bw; P<0.005). Induction of streptozotocin diabetes induced similar hyperglycemia (351±27 vs 387±30mg/dl; n=7), food/fluid intake as well as glucosuria (5.8±1.2 vs 4.5±1.4mmol/mg creatinine) in Sglt1−/− vs WT. The diabetes‐induced increase in GFR observed in WT (444±24 vs 373±17μl/min in control; P<0.05)(assessed in conscious mice by FITC inulin plasma kinetics) was lacking in Sglt1−/− (378±18 vs 417±19μl/min in control). Diabetes increased urinary H2O2 in WT (196±26nmol/mg) to levels observed in diabetic (196±11nmol/mg) or non‐diabetic Sglt1−/− (see above). Diabetes‐induced albuminuria was at least as pronounced in Sglt1−/− as in WT (5±1 to 17±3 vs 4±1 to 9±2μg/mg creatinine). In conclusion, SGLT1 is a determinant of renal glucose reabsorption, renal oxidative stress and kidney weight. The presence of SGLT1 does not significantly affect diabetes‐induced hyperglycemia or albuminuria but determines hyperfiltration.(NIH DK56248)