Endosomal SGLT1 and its possible role in the regulation of D-glucose uptake

Abstract

To elucidate the role of endosomal SGLTl in the regulation of sodium-dependent D-glucose uptake into enterocytes, we investigated the relationship between subcellular distribution of SGLTl and sodium-dependent 14C-methylglucose uptake into Caco-2 cells under varying conditions. Incubation with mastoparan shifted a large amount of SGLTl from the apical membrane to intracellular sites and significantly reduced sodiumdependent 14C-methylglucose uptake. We also investigated the effect of extracellular D-glucose levels. Cells pre-incubated with D-glucose free medium exhibited a significantly higher sodiumdependent 14C-methylglucose uptake than cells pre-incubated with high D-glucose medium. No difference in the overall subcellular distribution of SGLTl was observed between the two conditions. Interestingly, the change in 14C-methylglucose uptake was attenuated when microtubules were depolymerized. These results suggest that pharmacologically, D-glucose uptake can be regulated by a shift of the steady state distribution of carriers from the plasma membrane to endosomes. The physiological substrate D-glucose alters substrate uptake by an additional mechanism that requires microtubule-dependent vesicle transport without a change in the steady state distribution. This phenomenon could be explained by the hypothesis that SGLTl undergoes an activation/deactivation cycle during its constitutive cycling from endosomes to the plasma membrane and back