High glucose induces Glucose transporter‐2 (GLUT2), but not Na‐glucose cotransporter‐1 (SGLT1) mediated glucose absorption

Abstract

BackgroundGlucose dependent insulinotropic peptide (GIP) is a hormone that has a cyclic pathway in the stimulation of glucose transport. GIP increases transport of glucose, which in turn stimulates GIP secretion. This cycle increases the jejunal absorption of glucose, which stimulates insulin release. High glucose results in excess GIP secretion that causes unusually high glucose absorption and high blood glucose that stimulates insulin release that causes insulin insensitivity. Presence of high blood glucose and insulin lead to obesity and Type‐2 diabetes. Although SGLT1 is the primary apical glucose absorptive process, GLUT2 has been localized on the intestinal apical membranes of obese human and mouse models. However, signaling mechanisms of how GIP regulates glucose transporters in the presence of normal versus high levels of extracellular glucose concentrations is not known.HypothesisExtracellular glucose concentration that alters cellular GIP level would regulate glucose transporters on to the apical membrane of differentiated cells.MethodsIntestinal epithelial crypt cell‐6 (IEC6 cells) where grown 5‐days post confluent on transwell snapwells using standard DMEM media supplemented with 5% FBS and either 4.5 or 0.45 g/liter of glucose for high and low glucose, respectively. Mucosal to serosal (m‐s) glucose fluxes were measured across IEC6 cell layers that were mounted under voltage clamp conditions in Ussing chambers. Short circuit currents were measured to distinguish the SGLT1 (i.e. electrogenic) and GLUT2 (i.e. electroneutral) mediated glucose absorption. Apical membranes were isolated from IEC6 cell monolayers using a biotinylation technique. Western blot analyses were performed using SGLT1 and GLUT2 antibodies.ResultsGlucose absorption is substantially higher in IEC6 cells that were grown in high glucose medium compared to that grown in low glucose medium. In contrast to increased rate of glucose absorption, Isc is not significantly altered as an indication that high glucose increased GLUT2 mediated, but not SGLT1 mediated glucose absorption in IEC6 cells. Western blot analyses revealed that GLUT2, but not SGLT1 specific protein expression is increased on the apical membrane of IEC6 cells grown in the high glucose medium.ConclusionsHigh extracellular glucose environment stimulates GLUT2, but not SGLT1 expression and GLUT2 mediated glucose absorption in intestinal epithelial cells.SpeculationWe speculate that GLUT2 might be regulated similarly in in the villus cells of mouse intestine.Support or Funding InformationIMBRE grant #G110‐18‐W6619This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.