title: Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass.
abstract: 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.
authors.affiliation: Center for Basic and Translational Obesity Research, Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Nima
authors.initials: N
authors.lastname: Saeidi
authors.forename: Luca
authors.initials: L
authors.lastname: Meoli
authors.forename: Eirini
authors.initials: E
authors.lastname: Nestoridi
authors.forename: Nitin K
authors.initials: NK
authors.lastname: Gupta
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kvas
authors.forename: John
authors.initials: J
authors.lastname: Kucharczyk
authors.forename: Ali A
authors.initials: AA
authors.lastname: Bonab
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Fischman
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
authors.forename: Nicholas
authors.initials: N
authors.lastname: Stylopoulos
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002784:Cholesterol / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000601:surgery; D004063:Digestion; D004734:Energy Metabolism; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D015390:Gastric Bypass; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006019:Glycolysis; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D053858:Metabolic Networks and Pathways; D055432:Metabolomics; D064847:Multimodal Imaging; D010427:Pentose Phosphate Pathway; D049268:Positron-Emission Tomography; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D051272:Glucose Transporter Type 1; C495679:Slc2a1 protein, rat; D019788:Fluorodeoxyglucose F18; D002784:Cholesterol; D005947:Glucose