Review
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jul 14, 2006; 12(26): 4117-4129
Published online Jul 14, 2006. doi: 10.3748/wjg.v12.i26.4117
Gut hormones, and short bowel syndrome: The enigmatic role of glucagon-like peptide-2 in the regulation of intestinal adaptation
GR Martin, PL Beck, DL Sigalet
GR Martin, PL Beck, DL Sigalet, University of Calgary, Gastrointestinal Research Group, Calgary, Alberta T2N 4N1, Canada
Author contributions: All authors contributed equally to the work.
Supported by the Alberta Children’s Hospital Research Foundation
Correspondence to: Gary Martin, Department of Gastrointestinal Sciences, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW., Calgary, Alberta T2N 4N1, Canada. marting@ucalgary.ca
Telephone: +1-403-2203189 Fax: +1-403-2833840
Received: November 10, 2005
Revised: January 5, 2006
Accepted: January 14, 2006
Published online: July 14, 2006
Abstract

Short bowel syndrome (SBS) refers to the malabsorption of nutrients, water, and essential vitamins as a result of disease or surgical removal of parts of the small intestine. The most common reasons for removing part of the small intestine are due to surgical intervention for the treatment of either Crohn's disease or necrotizing enterocolitis. Intestinal adaptation following resection may take weeks to months to be achieved, thus nutritional support requires a variety of therapeutic measures, which include parenteral nutrition. Improper nutrition management can leave the SBS patient malnourished and/or dehydrated, which can be life threatening. The development of therapeutic strategies that reduce both the complications and medical costs associated with SBS/long-term parenteral nutrition while enhancing the intestinal adaptive response would be valuable.

Currently, therapeutic options available for the treatment of SBS are limited. There are many potential stimulators of intestinal adaptation including peptide hormones, growth factors, and neuronally-derived components. Glucagon-like peptide-2 (GLP-2) is one potential treatment for gastrointestinal disorders associated with insufficient mucosal function. A significant body of evidence demonstrates that GLP-2 is a trophic hormone that plays an important role in controlling intestinal adaptation. Recent data from clinical trials demonstrate that GLP-2 is safe, well-tolerated, and promotes intestinal growth in SBS patients. However, the mechanism of action and the localization of the glucagon-like peptide-2 receptor (GLP-2R) remains an enigma. This review summarizes the role of a number of mucosal-derived factors that might be involved with intestinal adaptation processes; however, this discussion primarily examines the physiology, mechanism of action, and utility of GLP-2 in the regulation of intestinal mucosal growth.

Keywords: Short bowel syndrome; Glucagon-like peptide-2; Epidermal growth factor; Insulin-like growth factor-I; Parenteral nutrition; Total parenteral nutrition; Intestinal adaptation; Intestinal mucosa; Gut hormones; Enteric nervous system