Fig. 1.

Maximum acute glucosuric response to sodium-glucose cotransporter SGLT2 inhibitor is enhanced 2-fold in Sglt1−/− vs. wild-type (WT) mice in metabolic cage studies. A: urinary glucose excretion (UGE) was greater in Sglt1−/− compared with WT mice following vehicle application. B: empagliflozin dose dependently increased UGE in WT. Please note different scale of y-axis vs. A. Compared with WT, the empagliflozin-induced UGE was shifted leftward and the maximum response doubled in Sglt1−/− mice. The difference between dose-response curves, which reflects the glucose reabsorption mediated via SGLT1 in WT mice, reached a maximum at a dose of ∼0.4 mg/kg (indicated at the left of the vertical lines) and was maintained (all vertical lines have same length) for higher doses up to 10 mg/kg, indicating a high selectivity of the SGLT2 inhibitor vs. SGLT1 in this dose range. Note that empagliflozin began to increase glucose excretion in WT when reabsorption via SGLT1 reached its maximum; n = 4–8/dose and genotype. *P < 0.05 vs. WT by ANOVA and unpaired Student's t-test.