Affiliation:
1. Department of Medicine, Banting and Best Diabetes Centre, The Toronto General Hospital, University of Toronto, Toronto, Canada M5G2C4
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)[Gly2]GLP-2 significantly improved survival whether administered before, concomitant with, or after indomethacin. h[Gly2]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[Gly2]GLP-2- vs. saline-treated controls). h[Gly2]GLP-2 significantly reduced cytokine induction, bacteremia, and the percentage of positive splenic and hepatic bacterial cultures ( P < 0.05). h[Gly2]GLP-2 enhanced epithelial proliferation ( P < 0.05 for increased crypt cell proliferation in h[Gly2]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.
Publisher
American Physiological Society
Subject
Physiology (medical),Physiology,Endocrinology, Diabetes and Metabolism
Cited by
161 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献