Effects of artificial sweeteners on glucagon-like peptide 1 secretion in GLUTag cells, an in vitro model of enteroendocrine cell

Abstract

Due to the rise in diabetes rates across the world, the enteroendocrine cells (EEC) of the small intestine have gathered much interest in recent years because of their roles in secreting the incretin hormones, glucagon‐like peptide 1 (GLP‐1) and glucose‐dependent insulinotropic peptide (GIP) in response to ingested carbohydrates. Both GLP‐1 and GIP promote insulin synthesis and secretion and therefore play an important role in controlling blood glucose levels. While glucose induced incretin secretion by EEC cells has been well established, the response of EEC cells to other dietary carbohydrates, such as the dissacharides, and non‐nutritive sweeteners, such as artificial sweeteners (AS), is less well understood. Thus, to investigate the effects of the AS, aspartame, acesfulfame‐K and Canderel® (1.4% aspartame;0.95% acesulfame‐k) and the disaccharides, maltose, sucrose, trehalose and lactose on GLP‐1 secretion, we used the mouse EEC line, GLUTag, a well established model of the L cell, which is predominantly found in the distal regions of the small intestine. GLUTag cells were incubated with the AS (at 0, 0.25, 0.4 and 5mM), and the disaccharides and glucose (at 0, 0.25, 0.5, 2.5, 5, 12.5, 25 and 50mM) for 2 hours at 37° C and the supernatant collected. GLP‐1 was measured from the supernatant using a GLP‐1 (Active) ELISA assay (EMD Millipore®, UK). Our results showed that at dietary relevant doses (0.25–5mM) the individual AS, aspartame and acesulfame‐k, and the AS mixture, Canderel® significantly induced GLP‐1 secretion in GLUTag cells when compared to baseline (except for 0.25mM acesulfame‐k) and values were similar to glucose‐induced GLP‐1 secretion. Cells incubated in a combination of Canderel® and glucose (0.4mM and 5mM) showed the highest secretion of GLP‐1; indicating a potential synergistic effect of AS and other nutrients in EEC function. Of the disaccharides tested, maltose showed a significant dose‐responsive increase in GLP‐1 secretion from 0–5mM with values nearly similar to glucose induced secretion over the same concentration range. Gene expression studies by RT‐PCR showed the sweet taste receptors (T1R3) and maltase‐glucoamylase (MGAM) gene to be expressed in the cell line; suggesting the potential mechanism behind AS and maltose sensing in EEC. These in vitro results indicate a possible role for AS and the disaccharide maltose in promoting incretin hormone secretion and having an impact on glycaemia. Support or Funding Information Self‐funded project This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.