Intestinal sweet-sensing pathways and metabolic changes after Roux-en-Y gastric bypass surgery.

Abstract

Studies suggest that improvements in type 2 diabetes (T2D) post- Roux-en-Y gastric bypass (RYGB) surgery are attributable to decreased intestinal glucose absorption capacity mediated by exclusion of sweet taste-sensing pathways in isolated proximal bowel. We probed these pathways in rat models that had undergone RYGB with catheter placement in the biliopancreatic (BP) limb to permit post-RYGB exposure of isolated bowel to sweet taste stimulants. Lean Sprague Dawley (n = 13) and obese Zucker diabetic fatty rats (n = 15) underwent RYGB with BP catheter placement. On postoperative day 11 (POD 11), rats received catheter infusions of saccharin [sweet taste receptor (T1R2/3) agonist] or saline (control). Jejunum was analyzed for changes in glucose transporter/sensor mRNA expression and functional sodium-glucose transporter 1 (SGLT1)-mediated glucose uptake. Saccharin infusion did not alter glucose uptake in the Roux limb of RYGB rats. Intestinal expression of the glucose sensor T1R2 and transporters (SGLT1, glucose transporter 2) was similar in saccharin- vs. saline-infused rats of both strains. However, the abundance of SGLT3b mRNA, a putative glucose sensor, was higher in the common limb vs. BP/Roux limb in both strains of bypassed rats and was significantly decreased in the Roux limb after saccharin infusion. We concluded that failure of BP limb exposure to saccharin to increase Roux limb glucose uptake suggests that isolation of T1R2/3 is unlikely to be involved in metabolic benefits of RYGB, as restimulation failed to reverse changes in intestinal glucose absorption capacity. The altered expression pattern of SGLT3 after RYGB warrants further investigation of its potential involvement in resolution of T2D after RYGB.