Vasoactive intestinal peptide is a local mediator in a gut-brain neural axis activating intestinal gluconeogenesis

Neurogastroenterol Motil. 2015 Mar;27(3):443-8. doi: 10.1111/nmo.12508. Epub 2015 Jan 13.

Abstract

Intestinal gluconeogenesis (IGN) promotes metabolic benefits through activation of a gut-brain neural axis. However, the local mediator activating gluconeogenic genes in the enterocytes remains unknown. We show that (i) vasoactive intestinal peptide (VIP) signaling through VPAC1 receptor activates the intestinal glucose-6-phosphatase gene in vivo, (ii) the activation of IGN by propionate is counteracted by VPAC1 antagonism, and (iii) VIP-positive intrinsic neurons in the submucosal plexus are increased under the action of propionate. These data support the role of VIP as a local neuromodulator released by intrinsic enteric neurons and responsible for the induction of IGN through a VPAC1 receptor-dependent mechanism in enterocytes.

Keywords: glucose-6-phosphatase; gut-brain axis; intestinal gluconeogenesis; vasoactive intestinal peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enteric Nervous System / metabolism*
  • Gluconeogenesis* / drug effects
  • Glucose-6-Phosphatase / metabolism*
  • Jejunum / drug effects
  • Jejunum / innervation
  • Jejunum / metabolism*
  • Male
  • Neurons / metabolism*
  • Rats, Sprague-Dawley
  • Receptors, Vasoactive Intestinal Polypeptide, Type I / metabolism
  • Vasoactive Intestinal Peptide / administration & dosage
  • Vasoactive Intestinal Peptide / metabolism*

Substances

  • Receptors, Vasoactive Intestinal Polypeptide, Type I
  • Vasoactive Intestinal Peptide
  • Glucose-6-Phosphatase