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

Abstract

Bhutta HY, Deelman TE, le Roux CW, Ashley SW, Rhoads DB, Tavakkoli A. Intestinal sweet-sensing pathways and metabolic changes after Roux-en-Y gastric bypass surgery. Am J Physiol Gastrointest Liver Physiol 307: G588 -G593, 2014. First published July 3, 2014 doi:10.1152/ajpgi.00405.2013.-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 ϭ 13) and obese Zucker diabetic fatty rats (n ϭ 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.Roux-en-Y gastric bypass; obesity; type 2 diabetes mellitus; intestinal sweet taste sensor; sodium-glucose transporter 1 IN RECENT DECADES, BARIATRIC SURGERY has evolved into the foremost therapy for obesity. Moreover, one of the weight loss operations, Roux-en-Y Gastric Bypass surgery (RYGB), is associated with a high rate of remission of type 2 diabetes mellitus (T2D), with an early and weight-independent mechanism that improves glucose homeostasis (2, 17). However, the mechanisms mediating the resolution of T2D remain poorly understood.Intense investigation of contributory factors has implicated several mechanisms, including alterations in incretin levels, the gut microbiome, bile acids, and an area of interest to our lab, namely intestinal nutrient sensing. The surgical isolation of duodenum and proximal jejunum appear to be critical in mediating resolution of T2D, supported by outcomes following endoluminal sleeve device insertion and surgical procedures (e.g., RYGB, biliopancreatic diversion), which exclude a sim...

Putative tissue location and function of the SLC5 family member SGLT3

“…Isolation of the proximal small intestine and its luminal glucose-sensing capacity from nutrients, combined with the presence of non-digested luminal nutrients in more distal parts of the small intestine, is thought to be crucial in the weight-reducing and anti-diabetic effects of surgery, although the mechanisms have not been defined. SGLT3b mRNA is expressed differentially along the small intestine after RYGB surgery in a rat model (Bhutta et al 2014). Expression was significantly higher in the common limb (distal to the Y-intersection) of both Sprague-Dawley and diabetic Zucker diabetic fatty rats compared with the biliopancreatic (bypassed portion of stomach and duodenum) and Roux limbs (anastomosis of fundal gastric remnant with jejunum).…”

“…Studies designed to differentiate between the two isoforms have detected expression in hypothalamus, kidney and duodenum in Sprague-Dawley rats (O'Malley et al 2006), whereas SGLT3b was also detected in jejunum and proximal ileum (Pal et al 2015). In addition, SGLT3b was detected in different parts of the jejunum after Roux-en-Y gastric bypass (RYGB) surgery in Sprague-Dawley and Zucker diabetic fatty rats (Bhutta et al 2014). In cell lines, expression was found in the intestinal endocrine GLUTag cell line (Gribble et al 2003) and in primary cultures of mouse cortical kidney cells (Tabatabai et al 2001).…”

“…In addition, SGLT3b was detected in different parts of the jejunum after Roux‐en‐Y gastric bypass (RYGB) surgery in Sprague–Dawley and Zucker diabetic fatty rats (Bhutta et al . ). In cell lines, expression was found in the intestinal endocrine GLUTag cell line (Gribble et al .…”

“…SGLT3b mRNA is expressed differentially along the small intestine after RYGB surgery in a rat model (Bhutta et al . ). Expression was significantly higher in the common limb (distal to the Y‐intersection) of both Sprague–Dawley and diabetic Zucker diabetic fatty rats compared with the biliopancreatic (bypassed portion of stomach and duodenum) and Roux limbs (anastomosis of fundal gastric remnant with jejunum).…”

“…Furthermore, infusion of saccharin, which stimulates taste receptors T1R2/3, into the biliopancreatic limb downregulated expression of SGLT3b in the common limb of Zucker diabetic fatty rats, though not significantly in Sprague–Dawley rats (Bhutta et al . ). These data suggest a possible role for SGLT3 in the post‐RYGB intestinal changes.…”