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Intestinal Gluconeogenesis Is a Key Factor for Early Metabolic Changes after Gastric Bypass but Not after Gastric Lap-Band in Mice

Institut National de la Sante et de la Recherche Medicale, U695, Faculté de Médecine Xavier Bichat, Universite Paris 7, Paris, F-75870, France.
Cell metabolism (Impact Factor: 17.57). 10/2008; 8(3):201-11. DOI: 10.1016/j.cmet.2008.08.008
Source: PubMed

ABSTRACT

Unlike the adjustable gastric banding procedure (AGB), Roux-en-Y gastric bypass surgery (RYGBP) in humans has an intriguing effect: a rapid and substantial control of type 2 diabetes mellitus (T2DM). We performed gastric lap-band (GLB) and entero-gastro anastomosis (EGA) procedures in C57Bl6 mice that were fed a high-fat diet. The EGA procedure specifically reduced food intake and increased insulin sensitivity as measured by endogenous glucose production. Intestinal gluconeogenesis increased after the EGA procedure, but not after gastric banding. All EGA effects were abolished in GLUT-2 knockout mice and in mice with portal vein denervation. We thus provide mechanistic evidence that the beneficial effects of the EGA procedure on food intake and glucose homeostasis involve intestinal gluconeogenesis and its detection via a GLUT-2 and hepatoportal sensor pathway.

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    • "On the other hand, gastric banding (a traditional therapy focused on weight loss through lifestyle change) (Madden et al. 2008) and an animal study based on restricted food intake (Pacheco et al. 2007) did not result in notable diabetes control. The foregut (Hickey et al. 1998), midgut (Troy et al. 2008), and hindgut (Thaler & Cummings 2009) hypotheses provide more likely explanations. The midgut hypothesis states that hyperplasia of the Roux-limb per se greatly increases glucose consumption. "
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