Journal
JOURNAL OF PARENTERAL AND ENTERAL NUTRITION
Volume 32, Issue 3, Pages 254-265Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0148607108316198
Keywords
intestinal failure; intestinal adaptation; Gl hormones; short bowel syndrome; bowel resection
Categories
Funding
- NIDDK NIH HHS [R01-DK-42835, T32 DK007665, T32-DK-07665, R01 DK042835] Funding Source: Medline
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Background: Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent proglucagon-derived hormone that stimulates intestinal adaptive growth. Our aim seas to determine whether exogenous GLP-2 increases resection-induced adaptation without diminishing endogenous proglucagon and GLP-2 receptor expression. Methods: Rats underwent transection or 70% jejunoileal resection +/- GLP-2 infusion (100 mu g/kg body weight/d) and were fed a semipurified diet With continuous infusion of GLP-2 or saline by means of jugular catheter. After 7 days, body weight, mucosal cellularity (dry mass, protein and DNA), crypt-villus height, and crypt cell proliferation (by bromodeoxyuridine staining) Were determined. Plasma bioactive GLP-2 (by radioimmunoassay), proglucagon and GLP-2 receptor mRNA expression (by Northern blot and real-time reverse transcriptase quantitative polymerase chain reaction) were measured. GLP-2 receptor was colocalized to neuroendocrine markers by immunohistochemistry Results: Low-dose exogenous GLP-2 increased mucosal cellularity and crypt-villus height in the duodenum, jejunum, and ileum; enterocyte proliferation in the jejunal crypt and duodenal and jejunal sucrase segmental activity. Plasma bioactive GLP-2 concentration increased 70% upon resection, with an additional 54% increase upon GLP-2 infusion in resected rats (P<.05). Heal proglucagon mRNA expression increased with resection, and exogenous ileum GLP-2 Failed to blunt this response. Exogenous GLP-2 increased ileum GLP-2 receptor expression 3-fold in resected animals and seas colocalized to vasoactive intestinal peptide-positive and endothelial nitric oxide synthase-expressing enteric neurons and serotonin-containing enteroendocrine cells in the jejunum and ileum of resected rats. Conclusions: Exogenous GLP-2 augments adaptive growth and digestive capacity of the residual small intestine in a rat model Of mid-small bowel resection by increasing plasma GLP-2 concentrations and GLP-2 receptor expression without diminishing endogenous proglucagon expression.
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