Glucagon-like peptide 2 decreases mortality and reduces the severity of indomethacin-induced murine enteritis.

Abstract

Glucagon-like peptides (GLPs) are secreted from enteroendocrine cells in the gastrointestinal tract. GLP-1 actions regulate blood glucose, whereas GLP-2 exerts trophic effects on intestinal mucosal epithelium. Although GLP-1 actions are preserved in diseases such as diabetes, GLP-2 action has not been extensively studied in the setting of intestinal disease. We have now evaluated the biological effects of a human GLP-2 analog in the setting of experimental murine nonsteroidal antiinflammatory drug-induced enteritis. Human (h)[Gly(2)]GLP-2 significantly improved survival whether administered before, concomitant with, or after indomethacin. h[Gly(2)]GLP-2-treated mice exhibited reduced histological evidence of disease activity, fewer intestinal ulcerations, and decreased myeloperoxidase activity in the small bowel (P < 0.05, h[Gly(2)]GLP-2- vs. saline-treated controls). h[Gly(2)]GLP-2 significantly reduced cytokine induction, bacteremia, and the percentage of positive splenic and hepatic bacterial cultures (P < 0.05). h[Gly(2)]GLP-2 enhanced epithelial proliferation (P < 0.05 for increased crypt cell proliferation in h[Gly(2)]GLP-2- vs. saline-treated mice after indomethacin) and reduced apoptosis in the crypt compartment (P < 0.02). These observations demonstrate that a human GLP-2 analog exerts multiple complementary actions that serve to preserve the integrity of the mucosal epithelium in experimental gastrointestinal injury in vivo.

• Authors: R P Boushey, B Yusta, D J Drucker
• Journal: The American journal of physiology (Am J Physiol) Vol. 277 Issue 5 Pg. E937-47 (11 1999) ISSN: 0002-9513 [Print] United States
• PMID: 10567023 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• (glycyl-glycyl)GLP-2
• Anti-Inflammatory Agents, Non-Steroidal
• Intercellular Signaling Peptides and Proteins
• Peptides
• Proliferating Cell Nuclear Antigen
• Glucagon
• Indomethacin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal
• Enteritis (chemically induced, drug therapy, mortality)
• Epithelial Cells (chemistry, pathology)
• Female
• Glucagon (physiology)
• Humans
• Ileum (chemistry, pathology)
• In Situ Nick-End Labeling
• Indomethacin
• Intercellular Signaling Peptides and Proteins
• Jejunum (chemistry, pathology)
• Mice
• Mice, Inbred Strains
• Peptides (pharmacology)
• Proliferating Cell Nuclear Antigen (analysis)
• Survival Analysis