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Gastroenterology Research and Practice
Volume 2010, Article ID 672453, 12 pages
http://dx.doi.org/10.1155/2010/672453
Research Article

The Effect of Glucagon-Like Peptide-2 Receptor Agonists on Colonic Anastomotic Wound Healing

1Division of Colorectal Surgery, Department of Surgery, Faculty of Medicine, University of Calgary, Calgary, AB, Canada T2N 1N4
2McCaig Institute for Bone and Joint Health, Department of Surgery, Faculty of Medicine, University of Calgary, Calgary, AB, Canada T2N 1N4
3Gastrointestinal Research Group and Division of Pediatric General Surgery, Department of Surgery, Faculty of Medicine, University of Calgary, Calgary, AB, Canada T2N 1N4
4Clinical Research and Development, Centocor Inc., Radnor, PA 19087-4557, USA
5Panum Institute, University of Copenhagen, 1165 Copenhagen, Denmark
6Department of Surgery, Alberta Children's Hospital, 2888 Shaganappi Trail NW, Calgary, AB, Canada T3B 6A8

Received 11 May 2010; Revised 23 July 2010; Accepted 29 July 2010

Academic Editor: Stanley Ashley

Copyright © 2010 Heather A. Redstone et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. Glucagon-like peptide 2 (GLP-2) is an intestinal specific trophic hormone, with therapeutic potential; the effects on intestinal healing are unknown. We used a rat model of colonic healing, under normoxic, and stress (hypoxic) conditions to examine the effect of GLP-2 on intestinal healing. Methods. Following colonic transection and reanastomosis, animals were randomized to one of six groups ( /group): controls, native GLP-2, long-acting GLP-2 (GLP-2- MIMETIBODY, GLP-2-MMB), animals were housed under normoxic or hypoxic (11%   ) conditions. Animals were studied five days post-operation for anastomotic strength and wound characteristics. Results. Anastomotic bursting pressure was unchanged by GLP-2 or GLP-2-MMB in normoxic or hypoxic animals; both treatments increased crypt cell proliferation. Wound IL-1 increased with GLP-2; IFN with GLP-2 and GLP-2-MMB. IL-10 and TGF- were decreased; Type I collagen mRNA expression increased in hypoxic animals while Type III collagen was reduced with both GLP-2 agonists. GLP-2 MMB, but not native GLP-2 increased TIMP 1-3 mRNA levels in hypoxia. Conclusions. The effects on CCP, cytokines and wound healing were similar for both GLP-2 agonists under normoxic and hypoxic conditions; anastomotic strength was not affected. This suggests that GLP-2 (or agonists) could be safely used peri-operatively; direct studies will be required.