title: The intestinal glucose-apelin cycle controls carbohydrate absorption in mice.
abstract: OBJECTIVE
  Glucose is absorbed into intestine cells via the sodium glucose transporter 1 (SGLT-1) and glucose transporter 2 (GLUT2); various peptides and hormones control this process. Apelin is a peptide that regulates glucose homeostasis and is produced by proximal digestive cells; we studied whether glucose modulates apelin secretion by enterocytes and the effects of apelin on intestinal glucose absorption.
  
  
  METHODS
  We characterized glucose-related luminal apelin secretion in vivo and ex vivo by mass spectroscopy and immunologic techniques. The effects of apelin on (14)C-labeled glucose transport were determined in jejunal loops and in mice following apelin gavage. We determined levels of GLUT2 and SGLT-1 proteins and phosphorylation of AMPKα2 by immunoblotting. The net effect of apelin on intestinal glucose transepithelial transport was determined in mice.
  
  
  RESULTS
  Glucose stimulated luminal secretion of the pyroglutaminated apelin-13 isoform ([Pyr-1]-apelin-13) in the small intestine of mice. Apelin increased specific glucose flux through the gastric epithelial barrier in jejunal loops and in vivo following oral glucose administration. Conversely, pharmacologic apelin blockade in the intestine reduced the increased glycemia that occurs following oral glucose administration. Apelin activity was associated with phosphorylation of AMPKα2 and a rapid increase of the GLUT2/SGLT-1 protein ratio in the brush border membrane.
  
  
  CONCLUSIONS
  Glucose amplifies its own transport from the intestinal lumen to the bloodstream by increasing luminal apelin secretion. In the lumen, active apelin regulates carbohydrate flux through enterocytes by promoting AMPKα2 phosphorylation and modifying the ratio of SGLT-1:GLUT2. The glucose-apelin cycle might be pharmacologically handled to regulate glucose absorption and assess better control of glucose homeostasis.
authors: INSERM Unité 1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France. cedric.dray@inserm.fr
authors: Cédric
authors: C
authors: Dray
authors: Yassine
authors: Y
authors: Sakar
authors: Claire
authors: C
authors: Vinel
authors: Daniele
authors: D
authors: Daviaud
authors: Bernard
authors: B
authors: Masri
authors: Luc
authors: L
authors: Garrigues
authors: Estelle
authors: E
authors: Wanecq
authors: Sylvain
authors: S
authors: Galvani
authors: Anne
authors: A
authors: Negre-Salvayre
authors: Larry S
authors: LS
authors: Barak
authors: Bernard
authors: B
authors: Monsarrat
authors: Odile
authors: O
authors: Burlet-Schiltz
authors: Philippe
authors: P
authors: Valet
authors: Isabelle
authors: I
authors: Castan-Laurell
authors: Robert
authors: R
authors: Ducroc
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D002241:Carbohydrates / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D011897:Random Allocation; D012016:Reference Values; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism
chemical_list: D002241:Carbohydrates; D051273:Glucose Transporter Type 2; D036341:Intercellular Signaling Peptides and Proteins; D051269:Sodium-Glucose Transporter 1; C495199:apelin-13 peptide; D005947:Glucose