Contribution of SGLT1 in cardiac glucose uptake

Abstract

The sodium-glucose transporter 1 (SGLT1) has been identified as the major SGLT isoform expressed in the heart. The exact role of this transporter in the heart is still unknown. Several authors have postulated a role on glucose transport using phlorizin as a specific inhibitor of SGLT transporters. However, high concentrations of phlorizin have been used in these studies and questions remain towards its potential effects on facilitated glucose transporters (GLUTs). Indeed, phlorizin has a similar structure to phloretin, GLUT-specific inhibitor and it could be hydrolyzed into phloretin acting on glucose transport independently of SGLT transporters. The aim of this study is to determine the contribution of SGLT1 transporter on glucose uptake in hearts and the impact of phlorizin on this uptake. We studied glucose uptake in vitro (cardiomyocytes), ex vivo (whole working hearts) and in vivo with SGLT1 WT and KO mice using 2- 3 [H]-glucose. Different phlorizin concentrations were tested to determine its impact on glucose uptake. We showed that glucose uptake was similar in SGLT1 WT and KO mice in basal, hyperglycemic and insulin-stimulated conditions. Moreover, we observed that high concentrations of phlorizin (10 −3 M) completely inhibit glucose uptake in cardiomyocytes subjected to insulin stimulation and that this inhibition was similar in WT and KO SGLT1 mice. An inhibition was also found at lower concentration of phlorizin (10 −4 M) to a lesser extent. The contribution of SGLT1 in glucose uptake in the heart is marginal compared to facilitate glucose uptake. At least at high concentrations, phlorizin inhibits glucose uptake independently of SGLT1 questioning the use of this compound to study SGLT-dependent glucose uptake.