IEC‐6 cells as a model to study non‐genomic responses of the small intestine

Lumenal exposure to 5 mM adenosine or adenosine 5′‐monophosphate‐2Na (AMP) rapidly (<10 min) and reversibly increases (~2‐fold) intestinal glucose uptake. Since intact tissues complicate attempts to explore the signaling networks and mechanisms for the responses, we sought a cultured cell model. Caco‐2 cells respond rapidly to adenosine, but the response is a 70% decrease in glucose uptake and is less for AMP (15% decrease). The differences between Caco‐2 cells and intact small intestine may be related to different tissue origins, so we explored the responses of the IEC‐6 cell line, which was established from the crypt cells of suckling rat small intestine. IEC‐6 cells were plated on Matrigel for 72 h to induce differentiation before exposure to 25 mM adenosine and AMP and measurement of accumulation of 4 μM glucose. Compared to control cells, 10 min exposure to 25 mM adenosine and AMP triggered similar increases in glucose uptake (307% and 322%, respectively). IEC‐6 cells cultured on plastic had a diminished response to adenosine, even after 72 h of exposure to cortisol to induce differentiation. Including 0.5 mM phloridzin in the uptake solution to inhibit SGLT1 reduced the increase in glucose accumulation by 45%, and the addition of phloretin to inhibit GLUT2 glucose uptake resulted in a further decline (75%). These findings suggest exposure of IEC‐6 cells to adenosine and AMP increase glucose uptake by upregulating SGLT1 and GLUT2. Therefore, differentiated IEC‐6 cells are a suitable model to investigate the signaling networks and mechanisms that are responsible for rapid non‐genomic changes in carrier‐mediated glucose uptake by the small intestine in response to exposure to adenosine, AMP, and other regulatory molecules.