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

Cell Metab. 2008 Sep;8(3):201-11. doi: 10.1016/j.cmet.2008.08.008.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dietary Fats / administration & dosage
  • Eating
  • Gastric Bypass*
  • Gastroplasty*
  • Gluconeogenesis*
  • Glucose / metabolism*
  • Glucose Transporter Type 1 / deficiency
  • Glucose Transporter Type 2 / deficiency
  • Insulin / blood
  • Insulin Resistance
  • Intestine, Small / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • Obesity, Morbid / metabolism*
  • Obesity, Morbid / surgery
  • Portal Vein / metabolism
  • Reproducibility of Results
  • Time Factors

Substances

  • Dietary Fats
  • Glucose Transporter Type 1
  • Glucose Transporter Type 2
  • Insulin
  • Slc2a1 protein, mouse
  • Slc2a2 protein, mouse
  • Glucose