Impaired Regulation of Renal K Elimination in Mice Lacking SGLT1

Sodium‐glucose transporter SGLT1 is expressed in the luminal membrane of late proximal tubules and further distal segments. We report impaired renal K excretion in Sglt1 knockout (−/−) mice as evidenced by renal K excretion that is not different from wild‐type (WT) mice despite of higher plasma concentrations of aldosterone and K (940±143 vs 277±42 pg/ml; 4.45±0.09 vs. 4.15±0.07 mM; P<0.05 ), which are major stimuli of renal K excretion. Significant differences in plasma aldosterone and K were maintained on high K diet but prevented by low K diet. Sglt1 −/− mice lost body weight compared with WT in response to a low and high K diet given for 6 days (−8.5±0.5 vs −4.4±0.7% of bw and −1.2±0.4 vs. 1.7±0.6% of bw; P<0.05 ). NADPH oxidase 2 (NOX2)‐derived reactive oxygen species (ROS) can inhibit ROMK channels in the distal nephron to lower renal K excretion. We found that urinary excretion of the more stable ROS, H 2 O 2 , was 10fold greater on low vs high K diet in WT but only varied by 3fold in Sglt1 −/− mice which, compared with WT, maintained higher levels under high K diet (25±4 vs 12±3 nmol H 2 O 2 /mg creatinine, P<0.05 ) but tended to have lower levels on low K diet. Renal Nox2 mRNA expression was 42% higher in Sglt1 −/− vs WT mice under control diet ( P<0.05 ). The studies link SGLT1 to renal H 2 O 2 excretion and K handling. Renal K excretion is not impaired in Sglt2 −/− mice supporting a specific role for SGLT1.