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Glucose Control Goes Out on a Limb
Roux-en-Y gastric bypass, a surgical procedure used to induce weight loss in morbidly obese patients, often leads to permanent remission of diabetes, even when patients regain weight. Studying a rat model, Saeidi et al. (p. 406; see Perspective by Berthoud) found that the surgically reconfigured intestinal segment (the Roux limb) underwent an adaptive response characterized by increased glucose uptake and utilization, apparently triggered by exposure to undigested nutrients. As a result of this change, the intestine provided a major tissue for whole-body glucose control. Whether the same adaptive response occurs in the human intestine remains to be examined.
The resolution of type 2 diabetes after Roux-en-Y gastric bypass (RYGB) attests to the important role of the gastrointestinal tract in glucose homeostasis. Previous studies in RYGB-treated rats have shown that the Roux limb displays hyperplasia and hypertrophy. Here, we report that the Roux limb of RYGB-treated rats exhibits reprogramming of intestinal glucose metabolism to meet its increased bioenergetic demands; glucose transporter-1 is up-regulated, basolateral glucose uptake is enhanced, aerobic glycolysis is augmented, and glucose is directed toward metabolic pathways that support tissue growth. We show that reprogramming of intestinal glucose metabolism is triggered by the exposure of the Roux limb to undigested nutrients. We demonstrate by positron emission tomography–computed tomography scanning and biodistribution analysis using 2-deoxy-2-[18F]fluoro-d-glucose that reprogramming of intestinal glucose metabolism renders the intestine a major tissue for glucose disposal, contributing to the improvement in glycemic control after RYGB.