Evidence for GLUT2-mediated glucose influx in rat Jejunum at low glucose concentration -

Abstract

Background: Intestinal glucose absorption is an integral component of overall glucose homeostasis. It occurs through active or facilitated mechanisms via the sodium dependent glucose transporter-1 (SGLT1) and sodium independent transporter-2 (GLUT2), depending on intraluminal glucose concentration. The study aims to characterize the relative contribution of SGLT1 and GLUT2 to glucose absorption under various glucose concentrations, in-vitro and in-vivo, and to investigate the possible control of glucose receptors by the extrinsic gastrointestinal innervation, in particular capsaicin sensitive primary afferents (CSPA).Methods: Glucose absorption was measured in-vivo by intraluminal perfusion of various concentrations of glucose in the jejunum of control rats and rats subjected to systemic CSPA fibers ablation or subdiaphragmatic vagotomy. 1-minute glucose uptake by jejunal strips was also measured in-vitro. The effects of adding various concentrations of phlorizin or phloretin, specific antagonists to SGLT1 and GLUT2, respectively, on glucose uptake were also studied in-vitro and in-vivo. The expression of SGLT1 and GLUT2 mRNA was determined in intestinal mucosal scrapings by real-time PCR.Results: Systemic desensitization to capsaicin decreased 1-minute glucose uptake (in-vitro) of 1 and 20 mM glucose by 55percent and 30percent (p0.001), respectively. However, it had no significant effect on the absorption of 50 mM glucose. The effect of selective inhibitors of SGLT1 and GLUT2 was more pronounced at lower concentration of glucose, and less effective in inhibiting glucose transport in rats subjected to CSPA fibers ablation. Systemic desensitization to capsaicin decreased basal absorption of 20 and 50 mM glucose in-vivo by 24percent (p0.01) and 40percent (p0.001) respectively. The addition of 1mM phloretin or phloridzin to the perfusate resulted in a decrease of absorption in both sham and CSPA ablated rats. This decrease was not significantly altered by CSPA ablation at 20 mM glucose. Furthermore, subdiaphragmatic vagotomy increased