Bile Diversion in Roux-en-Y Gastric Bypass Modulates Sodium-Dependent Glucose Intestinal Uptake

Gastro-intestinal exclusion by Roux-en-Y gastric bypass (RYGB) improves glucose metabolism, independent of weight loss. Although changes in intestinal bile trafficking have been shown to play a role, the underlying mechanisms are unclear. We performed RYGB in minipigs and showed that the intestinal uptake of ingested glucose is blunted in the bile-deprived alimentary limb (AL). Glucose uptake in the AL was restored by the addition of bile, and this effect was abolished when active glucose intestinal transport was blocked with phlorizin. Sodium-glucose cotransporter 1 remained expressed in the AL, while intraluminal sodium content was markedly decreased. Adding sodium to the AL had the same effect as bile on glucose uptake. It also increased postprandial blood glucose response in conscious minipigs following RYGB. The decrease in intestinal uptake of glucose after RYGB was confirmed in humans. Our results demonstrate that bile diversion affects postprandial glucose metabolism by modulating sodium-glucose intestinal cotransport. [Display omitted] •Glucose is absorbed only in the common limb in Roux-en-Y gastric bypass•Sodium-glucose co-transport is blunted in the bile-deprived alimentary limb•Sodium addition restores glucose uptake in the alimentary limb•Roux-en-Y gastric bypass decreases postprandial glucose response in humans The beneficial metabolic consequences of bariatric surgery independent of weight loss remain largely unexplained. Baud et al. identify sodium as a key factor and show that Roux-en-Y gastric bypass decreases the amount of sodium normally brought into the intestine with bile, thereby impairing intestinal glucose uptake via sodium-glucose cotransport.