A Single Dose of Oral Metformin Reduces the Post-Prandial Glucose Response Through a Transient Modulation of Apical Sodium-Glucose Co-Transporter
2019
Metformin (MET) is the most prescribed antidiabetic drug but its mechanism of action remains elusive. Recent clinical data point to the gut as MET primary target. In the present study we explored the effect of MET in the gut transport machinery. Using “in vitro” human enterocytes (Caco-2/TC7 cells) we showed that MET transiently reduced the apical density of sodium-glucose transporter 1 (SGLT1) and decreased the absorption of α-Methyl-D-1-glucopyranoside in an AMPK-independent manner, without changes in the post-translational signals. Administered 1hour before a glucose challenge in different animal models, MET reduced the postprandial glucose response (PGR). MET also reduced the urinary appearance of 2-(18F)-fluoro-2-deoxy-D-glucose after the intraluminal administration of the radiotracer. MET effect reducing PGR was maintained in glucose transporter type 2 (GLUT2)-KO mice but abrogated in (SGLT1)-KO animals. In conclusion, we unveiled the reversible effect of MET on SGLT1 trafficking, resulting in a transient decrease of the intestinal glucose absorption.
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