The therapeutic potential of targeting the glucagon-like peptide-2 receptor in gastrointestinal disease.

Abstract

INTRODUCTION:

Glucagon-like peptide-2 (GLP-2) is a pleiotropic intestinotrophic hormone that enhances digestive and absorptive capacity by acting through a limited population of intestinal GLP-2 receptors. The development of protease-resistant analogs or GLP-2/IgG fusion proteins confers a longer circulating half life than the native peptide. GLP-2 has garnered interest as a therapeutic most notably by reducing reliance on total parenteral nutrition in patients with short bowel syndrome.

AREAS COVERED:

The clinical evidence for benefit in conditions requiring longer term treatment with GLP-2 receptor agonists, for example short bowel syndrome and inflammatory bowel disease. Benefits of short-term GLP-2 treatment are emerging in pre-clinical models, such as post-operative ileus, GI mucositis and conditions of altered intestinal permeability. The therapeutic utility of GLP-2 receptor agonists is limited by concern that it predisposes patients to gastrointestinal cancers, or their re-occurrence in cancer patients. This affects the types of diseases treated and, possibly, the duration of dosing.

EXPERT OPINION:

GLP-2 is therapeutically attractive in diseases to enhance absorptive capacity, restore mucosal health and reduce inflammation. Long-term surveillance studies with a marketed therapeutic agent are needed to weigh the benefits of GLP-2 treatment against the potential effects on co-morbidities and increased risk of intestinal carcinogenesis.

• Authors: Pamela J Hornby, Beverley A Moore
• Journal: Expert opinion on therapeutic targets (Expert Opin Ther Targets) Vol. 15 Issue 5 Pg. 637-46 (May 2011) ISSN: 1744-7631 [Electronic] England
• PMID: 21314232 (Publication Type: Journal Article, Review)

Chemical References

• Glucagon-Like Peptide 2
• Glucagon-Like Peptide-2 Receptor
• Receptors, Glucagon

Topics

• Animals
• Gastrointestinal Diseases (drug therapy)
• Glucagon-Like Peptide 2 (physiology)
• Glucagon-Like Peptide-2 Receptor
• Humans
• Ileus (drug therapy)
• Inflammatory Bowel Diseases (drug therapy)
• Mucositis (drug therapy)
• Receptors, Glucagon (agonists, physiology)
• Short Bowel Syndrome (drug therapy)