| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Dept of Surgery, III Institute and GI Research, University of Calgary, Calgary, Canada
2 Medicine, III Institute, University of Calgary, Calgary, Canada
3 Department of Medical Physiology, The Panum Institute, University of Copenhagen, Copenhagen,, Denmark
4 Gastrointestinal Sciences/Surgery, University of Calgary, Calgary, Canada
5 Pediatric Surgery, Kagoshima University, Kagoshima, Japan
6 Surgery, III Institute, Faculty of Medicine, University of Calgary, Calgary, Canada
7 Dept. of Physiology & Biophysics, University of Calgary, Calgary, Canada
* To whom correspondence should be addressed. E-mail: sigalet{at}ucalgary.ca.
Glucagon-like peptide-2 (GLP-2) is an important regulator of nutritional absorptive capacity with anti-inflammatory actions. We hypothesized that GLP-2 reduces intestinal mucosal inflammation by activation of vasoactive intestinal polypeptide (VIP) neurons of the submucosal plexus. Ileitis or colitis was induced in rats by injection of trinitrobenzene sulfonic acid (TNBS), or colitis by administration of dextran sodium sulphate (DSS) in drinking water. Subsets of animals received (1-33) GLP-2 (50 µg/kg s.c. bid) either immediately, or 2 days following the establishment of inflammation and were followed for 3-5 days. The involvement of VIP neurons was assessed by concomitant administration of GLP-2 and the VIP antagonist VIP 7-28-Neurotensin-6-11 and by immunohistochemical labelling of GLP-2 activated neurons. In all models, GLP-2 treatment, whether given immediately, or delayed until inflammation was established, resulted in significant improvements in animal weights, mucosal inflammation indices (myeloperoxidase levels, histological mucosal scores) and reduced levels of inflammatory cytokines (IFN
, TNF
, IL-1
) and iNOS, with increased levels of IL-10 in TNBS-ileitis and DSS-colitis. Reduced rates of crypt cell proliferation and in apoptosis within crypts in inflamed tissues were also noted with GLP-2 treatment. These effects were abolished with co-administration of GLP-2 and the VIP antagonist. GLP-2 was shown to activate neurons and increase the number of cells expressing VIP in the submucosal plexus of the ileum. These findings suggest that GLP-2 acts as an anti-inflammatory agent through activation of enteric VIP neurons, independent of proliferative effects. They support further studies of the role of neural signalling in the regulation of intestinal inflammation.
This article has been cited by other articles:
|
|
 |
|
  S. Baldassano, S. Liu, M.-H. Qu, F. Mule, and J. D. Wood Glucagon-like peptide-2 modulates neurally evoked mucosal chloride secretion in guinea pig small intestine in vitro Am J Physiol Gastrointest Liver Physiol, October 1, 2009; 297(4): G800 - G805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Amato, S. Baldassano, R. Serio, and F. Mule Glucagon-like peptide-2 relaxes mouse stomach through vasoactive intestinal peptide release Am J Physiol Gastrointest Liver Physiol, March 1, 2009; 296(3): G678 - G684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. A. Ivory, L. E. Wallace, D.-M. McCafferty, and D. L. Sigalet Interleukin-10-independent anti-inflammatory actions of glucagon-like peptide 2 Am J Physiol Gastrointest Liver Physiol, December 1, 2008; 295(6): G1202 - G1210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Tappenden Inflammation and Intestinal Function: Where Does It Start and What Does It Mean? JPEN J Parenter Enteral Nutr, November 1, 2008; 32(6): 648 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Koopmann, D. W. Nelson, S. G. Murali, X. Liu, M. S. Brownfield, J. J. Holst, and D. M. Ney Exogenous Glucagon-Like Peptide-2 (GLP-2) Augments GLP-2 Receptor mRNA and Maintains Proglucagon mRNA Levels in Resected Rats JPEN J Parenter Enteral Nutr, May 1, 2008; 32(3): 254 - 265. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
