Stress impairs murine intestinal barrier function: improvement by glucagon-like peptide-2.
Stress-induced intestinal barrier dysfunction may be involved in chronic intestinal disorders. Glucagon-like peptide-2 (GLP-2) is an intestinotrophic growth hormone that can rapidly improve intestinal epithelial barrier function. Here, we investigated whether mouse intestine is responsive to chronic psychological stress and whether pretreatment with GLP-2 can ameliorate stress-induced changes. Mice were subjected to water avoidance stress (WAS; 1 h/day for 10 days) with GLP-2 or saline administered 4 h before each WAS session. After the final stress period, the intestine was removed for assessment of physiological/morphological changes. Compared with controls (sham-stressed mice), stressed mice demonstrated enhanced ion secretion and permeability in the jejunum, ileum, and colon. In addition, increased numbers of bacteria were observed adhering to and/or penetrating the epithelium, associated with infiltration of mononuclear cells into the mucosa. GLP-2 treatment improved intestinal barrier function in stressed mice and ameliorated other aspects of impaired host defense. Our study extends previous findings in rats of stress-induced intestinal dysfunction and provides insights into potential novel therapeutics.
Cameron
Heather L
HL
Intestinal Disease Research Programme, McMaster University, Hamilton, ON, Canada L8N 3Z5.
Perdue
Mary H
MH
D000818:Animals; D001424:Bacterial Infections / Q000276:immunology; D001835:Body Weight / Q000187:drug effects; D003106:Colon / Q000473:pathology; D015194:Diffusion Chambers, Culture; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D006735:Horseradish Peroxidase / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D007422:Intestines / Q000187:drug effects / Q000503:physiopathology* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D013315:Stress, Psychological / Q000188:drug therapy / Q000503:physiopathology*
D053767:Glucagon-Like Peptide 2; D010455:Peptides; D004763:Glucagon-Like Peptides; D006735:Horseradish Peroxidase