Sodium-Glucose Transporter-2 (SGLT2; SLC5A2) Enhances Cellular Uptake of Aminoglycosides
Figure 7
Phlorizin decreased renal GTTR uptake, and increased serum drug levels in vivo.
(A) In Sglt2+/− mice, rabbit anti-SGLT2 immunolabeling was predominantly localized at the apical, lumenal region of proximal tubules (p), with negligible labeling in distal tubules (d). (B) GTTR fluorescence was most intense (as saturated puncta) in the apical region of proximal tubules (p), with less intense diffuse labeling in the cytoplasm of these same cells. Very weak and only diffuse GTTR fluorescence was observed in the cytoplasm of distal tubule cells (d). (C) Merged image showing colocalization of SGLT2 (green) and GTTR (red) in proximal tubules. (D–F) When Sglt2+/− mice were pre-treated with phlorizin, significantly reduced GTTR fluorescence was observed in the cytoplasm and apical brush border (arrows) of proximal tubule cells (E) compared to untreated mice (D, F; **p<0.01). (G, I) In Sglt2−/− mice, GTTR fluorescence was diffusely distributed throughout the cytoplasm of proximal tubule cells, with intense fluorescence at the apical brush border. (H, I) Phlorizin had no effect on the uptake, distribution or intensity of GTTR fluorescence in Sglt2−/− proximal tubule cells (**p<0.01). Scale bar = 20 µm. (J, K) In Sglt2+/− mice, phlorizin pre-treatment significantly increased both gentamicin and GTTR serum levels compared to vehicle treated control mice (*p<0.05). In Sglt2−/− mice, phlorizin did not significantly change gentamicin or GTTR serum levels. However, serum levels of gentamicin or GTTR serum level were significantly higher in Sglt2−/− mice than in Sglt2+/− mice in the absence of phlorizin treatment (*p<0.05).