Abstract
Proximal tubules (PTs) take up most of the glucose in the glomerular filtrate and return it to peritubular capillary blood. Sodium-glucose cotransporter 2 (SGLT2) at the apical membrane takes up glucose into the cell. Glucose then flows across the cells and is transported to the interstitium via glucose transporter 2 (GLUT2) at the basolateral membrane. However, glucose transport under SGLT2 inhibition remains poorly understood. In this study, we evaluated the dynamics of a fluorescent glucose analog, 2-NBDG, in the PTs of live mice treated with or without the SGLT2 inhibitor, luseogliflozin. We employed real-time multiphoton microscopy, in which insulin enhanced 2-NBDG uptake in skeletal muscle. Influx and efflux of 2-NBDG in PT cells were compared under hypo-, normo-, and hyperglycemic conditions. Luseogliflozin did not exert significant effects on glucose influx parameters under any level of blood glucose. Our results suggest that blood glucose level per se does not alter glucose influx or efflux kinetics in PTs. In conclusion, neither SGLT2 inhibition nor blood glucose level affect glucose uptake kinetics in PTs. The former was because of glucose influx through basolateral GLUT2, which is an established bidirectional transporter.
Highlights
In modern life, owing to improvements in living conditions and enrichment of food types, excessive energy intake has created new challenges that threaten the health of individuals
In our previous study using intravital imagmatically reduced glucose uptake into the proximal tubules of mice treated with luseogliing at a subcellular spatial resolution, we found that glucose transporter 2 (GLUT2) downregulation dramatically flozin, a Sodium-glucose cotransporter 2 (SGLT2) inhibitor [7]
SGLT2 inhibitors, a novel class of drug used for treatment of diabetes, increase urinary glucose excretion by inhibiting the major glucose transporter in the kidney, SGLT2, thereby controlling the blood glucose level [1]
Summary
In modern life, owing to improvements in living conditions and enrichment of food types, excessive energy intake has created new challenges that threaten the health of individuals. In our previous study using intravital imagmatically reduced glucose uptake into the proximal tubules of mice treated with luseogliing at a subcellular spatial resolution, we found that GLUT2 downregulation dramatically flozin, a SGLT2 inhibitor [7]. This observation suggested the potential for glucose uptake reduced glucose uptake into the proximal tubules of mice treated with luseogliflozin, a by GLUT2 in the kidney under the influence of SGLT2 inhibitors This prompted our inSGLT2 inhibitor [7]. This observation suggested the potential for glucose uptake by GLUT2 terest in determining inhibition using luseogliflozin affects glucose upin the kidney under thewhether influenceSGLT2 of SGLT2 inhibitors This prompted our interest in detertake dynamics in the proximal tubule cells of live mice. (2-NBDG) in vivo and 2-deoxyglucose in vitro to visualize glucose dynamics
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