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Hypertension is exacerbated in diabetic patients because of increased salt retention. The aim of the present study is to determine whether enhanced SGLT2 function accounts for salt retention in diabetic mice.

Design and Method:

2-month type 2 diabetic db/db mice and their lean db/+ littermates were fed with normal (0.4% NaCl, ND) or high salt (8% NaCl, HS) diet for 6 months. The expression of SGLT2 was assayed by quantitative real-time PCR and western blot, and the acute SGLT2 activity assay was performed using treatment of a SGLT2 inhibitor, dapagliflozin (1mg/kg body weight), after glucose substitution (2 g/kg body weight) in the metabolic cages. The 24h-urinary sodium excretion and glycosuria were detected.


The body weight, fasting blood glucose and systolic blood pressure were higher in db/db mice than in db/+ mice. High salt intake not only increased systolic blood pressure and natriuresis, but also enhanced urinary volume and glycosuria in db/db mice (urinary volume: db/+ 186% vs. db/db 67%; urinary sodium excretion: db/+ 142% vs. db/db 57%). The renal SGLT2 mRNA and protein expression were noticeably higher in db/db mice than in db/+ mice, which can be down-regulated by high sodium intake. In response to dapagliflozin treatment, high sodium intake increased natriuresis and glycosuria to a much lesser extent in db/db mice than in db/+ mice (urinary sodium excretion increase: db/+ 170% vs. db/db 79%; urinary glucose excretion increase: db/+ 43% vs. db/db 15%).


These results indicate that high sodium intake-induced natriuresis is hampered in diabetic mice and a reduction in natriuresis due to increased SGLT2 activity occurred in diabetes under high sodium intake.

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