Upregulation of intestinal glucose transporters after Roux-en-Y gastric bypass to prevent carbohydrate malabsorption

Abstract

Objective: To determine the effect of Roux-en-Y gastric bypass (RYGB) on the expression of intestinal sweet taste receptors (STRs), glucose transporters (GTs), glucose absorption, and glycemia. Methods: Intestinal biopsies were collected for mRNA expression of STR (T1R2) and GTs (SGLT-1 and GLUT2) from 11 non-diabetic RYGB, 13 non-diabetic obese, and 11 healthy subjects, at baseline and following a 30 min small intestinal (SI) glucose infusion (30 g/150 ml water with 3 g 3-O-methyl-D-glucopyranose (3-OMG)). Blood glucose, plasma 3-OMG, and insulin were measured for 270 min. Results: In RYGB patients, expression of both GTs was 2-fold higher at baseline and after glucose infusion than those of morbidly obese or healthy subjects (P < 0.001). STR expressions were comparable amongst the groups. Peak plasma 3-OMG in both RYGB (r 5 0.69, P 5 0.01) and obese (r 5 0.72, P 5 0.005) correlated with baseline expression of SGLT-1, as was the case with peak blood glucose in RYGB subjects (r 5 0.69, P 5 0.02). Conclusions: The upregulated intestinal GTs in RYGB patients are associated with increased glucose absorption when glucose is delivered at a physiological rate, suggesting a molecular adaptation to prevent carbohydrate malabsorption from rapid intestinal transit after RYGB.

Nutrient Transporter Expression in the Jejunum in Relation to Body Mass Index in Patients Undergoing Bariatric Surgery

“…However, prior studies have indicated some differences worth noting between healthy lean, healthy obese, and morbidly obese patients. For example, a prior study revealed a higher expression of GLUT2 and SGLT1 in morbidly obese patients undergoing a Roux-en-Y gastric bypass compared to healthy normal weight people [25]. However, the biopsies in the controls were acquired from the distal duodenum, whereas in the morbidly obese patients the biopsies were acquired from the jejunum [25].…”

“…For example, a prior study revealed a higher expression of GLUT2 and SGLT1 in morbidly obese patients undergoing a Roux-en-Y gastric bypass compared to healthy normal weight people [25]. However, the biopsies in the controls were acquired from the distal duodenum, whereas in the morbidly obese patients the biopsies were acquired from the jejunum [25]. Moreover, the same study reported that bariatric surgery increased the expression of GLUT2 and SGLT1 , perhaps in an attempt to reduce carbohydrate malabsorption [25].…”

“…However, the biopsies in the controls were acquired from the distal duodenum, whereas in the morbidly obese patients the biopsies were acquired from the jejunum [25]. Moreover, the same study reported that bariatric surgery increased the expression of GLUT2 and SGLT1 , perhaps in an attempt to reduce carbohydrate malabsorption [25]. In another study, the duodenal expression of SGLT1 was higher in patients with morbid obesity compared to healthy controls and was associated with higher glucose absorption and incretin levels [26].…”

Bariatric surgery and obesity: influence on the incretins

“…33 The enhanced GLP-1 release after RYGBP is blunted if the meal is administered directly in the gastric remnant 39,40 or at a slow rate directly in the jejunal alimentary limb. 41 Recovery of the incretin effect after RYGBP The incretin effect, blunted in patients with type 2 diabetes, 20 was shown to increase to levels of normal glucose tolerant individuals 1 month after RYGBP in patients who underwent diabetes remission. 29 However, the incretin effect was not restored in weight-matched subjects who underwent equivalent 10% total weight loss by calorie restriction, demonstrating that the improvement in the incretin effect after RYGBP is weight loss independent.…”

Longer-Term Physiological and Metabolic Effects of Gastric Bypass Surgery

“…A study from Cavin et al [83] lends additional support to the view that gastric bypass causes intestinal hypertrophy and shows that glucose absorption is elevated and glucose becomes trapped within the intestinal epithelial cells. Finally a study from Nguyen et al [84] reports elevated GLUT-1 and 2 expression in the intestine following surgery. This increased expression could facilitate increased glucose absorption following surgery, and thus prevent carbohydrate malabsorption.…”