| Glucagon-like peptide-2 induces intestinal adaptation in parenterally fed rats with short bowel syndrome. | |
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MedLine Citation:
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PMID: 14962847 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glucagon-like peptide-2 (GLP-2) is an intestinal trophic enteroendocrine peptide that is associated with intestinal adaptation following resection. Herein, we investigate the effects of GLP-2 in a total parenteral nutrition (TPN)-supported model of experimental short bowel syndrome. Juvenile Sprague-Dawley rats underwent a 90% small intestinal resection and jugular catheter insertion. Rats were randomized to three groups: enteral diet and intravenous saline infusion, TPN only, or TPN + 10 microg.kg(-1).h(-1) GLP-2. Nutritional maintenance was isocaloric and isonitrogenous. After 7 days, intestinal permeability was assessed by quantifying the urinary recovery of gavaged carbohydrate probes. The following day, animals were euthanized, and intestinal tissue was processed for morphological and crypt cell proliferation (CCP) analysis, apoptosis (caspase-3), and expression of SGLT-1 and GLUT-5 transport proteins. TPN plus GLP-2 treatment resulted in increased bowel and body weight, villus height, intestinal mucosal surface area, CCP, and reduced intestinal permeability compared with the TPN alone animals (P < 0.05). GLP-2 treatment induced increases in serum GLP-2 levels and intestinal SGLT-1 expression (P < 0.01) compared with either TPN or enteral groups. No differences were seen in the villus apoptotic index between resection groups. Enterally fed resected animals had a significant decrease in crypt apoptotic indexes compared with nontreated animals. This study demonstrates that GLP-2 alone, without enteral feeding, stimulates indexes of intestinal adaptation. Secondly, villus hypertrophy associated with adaptation was predominantly due to an increase in CCP and not to changes in apoptotic rates. Further studies are warranted to establish the mechanisms of action and therapeutic potential of GLP-2. |
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Authors:
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Gary R Martin; Laurie E Wallace; David L Sigalet |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2004-02-12 |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: 286 ISSN: 0193-1857 ISO Abbreviation: Am. J. Physiol. Gastrointest. Liver Physiol. Publication Date: 2004 Jun |
Date Detail:
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Created Date: 2004-05-10 Completed Date: 2004-06-10 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
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Languages: eng Pagination: G964-72 Citation Subset: IM |
Affiliation:
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University of Calgary, Gastrointestinal Research Group, Calgary, Alberta, Canada, T2T 5C7. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adaptation, Physiological* Animals Caspase 3 Caspases / metabolism Cell Division / drug effects Enzyme Activation Glucagon-Like Peptide 2 Glucagon-Like Peptides Humans Ileum / pathology Intestinal Absorption Intestinal Mucosa / pathology Intestines / drug effects*, physiopathology* Male Membrane Glycoproteins / metabolism Monosaccharide Transport Proteins / metabolism Parenteral Nutrition, Total* Peptides / pharmacology* Permeability Rats Rats, Sprague-Dawley Recombinant Proteins / pharmacology Short Bowel Syndrome / pathology, physiopathology*, therapy* Sodium-Glucose Transporter 1 |
| Chemical | |
Reg. No./Substance:
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0/Glucagon-Like Peptide 2; 0/Membrane Glycoproteins; 0/Monosaccharide Transport Proteins; 0/Peptides; 0/Recombinant Proteins; 0/SLC5A1 protein, human; 0/Slc5a1 protein, rat; 0/Sodium-Glucose Transporter 1; 62340-29-8/Glucagon-Like Peptides; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
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