QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by L'Heureux, M.-C. Articles by Brubaker, P. L. Search for Related Content PubMed PubMed Citation Articles by L'Heureux, M.-C. Articles by Brubaker, P. L.

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Glucagon-Like Peptide-2 and Common Therapeutics in a Murine Model of Ulcerative Colitis

Departments of Physiology (M.-C.L'H., P.L.B.) and Medicine (P.L.B.), University of Toronto, Toronto, Ontario, Canada

The intestinal hormone glucagon-like peptide-2 (GLP-2) enhances bowel growth and reduces the severity of colonic injury in dextran sulfate sodium (DSS)-induced colitis in mice. In humans, ulcerative colitis is normally treated with aminosalicylates (ASAs) and corticosteroids (CSs) to reduce inflammation. However, whether the intestinotropic effects of GLP-2 are altered when combined with ASAs and/or CSs has not previously been explored. Thus, each agent [vehicle, ASA (sulfasalazine), CS (methylprednisolone), and ASA + CS] was administered alone or with GLP-2 to normal mice or mice with 3.5% DSS in the drinking water, for 10 consecutive days. GLP-2 treatment of DSS-mice increased survival and small intestinal weight (p < 0.05), and decreased body weight loss and colonic damage (p < 0.05). Furthermore, GLP-2 increased the number of proliferating cells in the colonic crypts of DSS-mice (p < 0.05). Administration of ASA, CS, or ASA + CS alone did not affect growth of the intestine in DSS-mice. However, administration of GLP-2 in combination with ASA was permissive for the beneficial effects of GLP-2 on survival and colonic damage, whereas CS treatment prevented these effects of GLP-2. Concomitant administration of GLP-2 with ASA + CS resulted in intermediate effects. No differences between colonic myeloperoxidase activity or IB levels (an inhibitor of the nuclear factor-B pro-inflammatory pathway) were found for any of these therapeutic agents. When taken together, the ability of GLP-2 to protect colonic mucosal architecture in DSS-colitis, and its effectiveness when given in combination with ASA, but not with CS, suggests a novel approach for the treatment of patients with colitis.

Address correspondence to: Dr. Patricia L. Brubaker, Department of Physiology, University of Toronto, Medical Sciences Building, Room 3366, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. E-mail: p.brubaker{at}utoronto.ca

This article has been cited by other articles:

				P. E. Dube, K. J. Rowland, and P. L. Brubaker Glucagon-Like Peptide-2 Activates -Catenin Signaling in the Mouse Intestinal Crypt: Role of Insulin-Like Growth Factor-I Endocrinology, January 1, 2008; 149(1): 291 - 301. [Abstract] [Full Text] [PDF]

				D. L. Sigalet, L. E. Wallace, J. J. Holst, G. R. Martin, T. Kaji, H. Tanaka, and K. A. Sharkey Enteric neural pathways mediate the anti-inflammatory actions of glucagon-like peptide 2 Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G211 - G221. [Abstract] [Full Text] [PDF]

				Y. Anini, A. Izzo, G. Y. Oudit, P. H. Backx, and P. L. Brubaker Role of phosphatidylinositol-3 kinase-{gamma} in the actions of glucagon-like peptide-2 on the murine small intestine Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1599 - E1606. [Abstract] [Full Text] [PDF]

				P. L. Brubaker and D. J. Drucker Minireview: Glucagon-Like Peptides Regulate Cell Proliferation and Apoptosis in the Pancreas, Gut, and Central Nervous System Endocrinology, June 1, 2004; 145(6): 2653 - 2659. [Abstract] [Full Text] [PDF]