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Glucagon-like peptide-2 induces a specific pattern of adaptation in remnant jejunum.
Dig Dis Sci. 2006 Sep; 51(9):1557-66.DD

Abstract

Glucagon-like peptide-2 (GLP-2) is an enteroendocrine hormone which is uniquely trophic for the intestine; a physiological role in regulating nutrient absorptive capacity is becoming apparent. GLP-2, independent of enteral feeding, stimulates a classical pattern of intestinal adaptation in terminal ileum following resection. Herein we investigate the effects of GLP-2 on the jejunal remant using a rat model of short bowel syndrome (SBS). Juvenile 250- to 275-g SD rats underwent 80% distal small bowel resection, leaving 20 cm of proximal jejunum and venous catheterization. Animals were maintained with total parenteral nutrition (TPN) or TPN+10 microg/kg/hr GLP-2 (n=8 per group). After 7 days, intestinal permeability was assessed by urinary recovery of gavaged carbohydrate probes. Animals were euthanized, and the intestines taken for analysis of morphology, crypt cell proliferation, apoptosis, and expression of SGLT-1 and GLUT-5 transport proteins. GLP-2 treatment reduced intestinal permeability and increased in vivo glucose absorption, small intestinal weight, surface area, villus height, crypt depth, and microvillus height. Intestinal mucosal DNA and protein content per unit length of the small bowel were increased (P < 0.05 for all comparisons). However, in contrast to previous studies examining GLP-2's effects on remnant ileum, the jejunal crypt apoptotic index was increased in GLP-2-treated animals, with no increase in SGLT-1 or GLUT 5 expression. These results show that exogenous GLP-2 treatment of animals with jejunal remnant reduces intestinal permeability, increases glucose absorption, and stimulates morphological features of intestinal adaptation including increased micovillus height and surface area. However, the pattern of changes seen is different from that in remnant ileum. This suggests that GLP-2's effects are specific to different regions of the bowel. Nonetheless, remnant jejunum is responsive to GLP-2 in the absence of enteral nutrition. Further studies are warranted to establish the mechanisms of action and therapeutic potential of GLP-2 in modulating nutrient absorptive capacity.

Authors+Show Affiliations

Sigalet DL
University of Calgary, Gastrointestinal Research Group, Calgary, Alberta, Canada. sigalet@ucalgary.ca
Bawazir O
No affiliation info available
Martin GR
No affiliation info available
Wallace LE
No affiliation info available
Zaharko G
No affiliation info available
Miller A
No affiliation info available
Zubaidi A
No affiliation info available

MeSH

Adaptation, PhysiologicalAnimalsApoptosisCaspase 3CaspasesCell ProliferationDisease Models, AnimalGlucagon-Like Peptide 2Glucagon-Like PeptidesGlucose Transporter Type 5IleumIntestinal AbsorptionIntestinal MucosaJejunumMaleRatsRats, Sprague-DawleyShort Bowel Syndrome

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16927140

Citation

Sigalet, D L., et al. "Glucagon-like Peptide-2 Induces a Specific Pattern of Adaptation in Remnant Jejunum." Digestive Diseases and Sciences, vol. 51, no. 9, 2006, pp. 1557-66.
Sigalet DL, Bawazir O, Martin GR, et al. Glucagon-like peptide-2 induces a specific pattern of adaptation in remnant jejunum. Dig Dis Sci. 2006;51(9):1557-66.
Sigalet, D. L., Bawazir, O., Martin, G. R., Wallace, L. E., Zaharko, G., Miller, A., & Zubaidi, A. (2006). Glucagon-like peptide-2 induces a specific pattern of adaptation in remnant jejunum. Digestive Diseases and Sciences, 51(9), 1557-66.
Sigalet DL, et al. Glucagon-like Peptide-2 Induces a Specific Pattern of Adaptation in Remnant Jejunum. Dig Dis Sci. 2006;51(9):1557-66. PubMed PMID: 16927140.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glucagon-like peptide-2 induces a specific pattern of adaptation in remnant jejunum. AU - Sigalet,D L, AU - Bawazir,O, AU - Martin,G R, AU - Wallace,L E, AU - Zaharko,G, AU - Miller,A, AU - Zubaidi,A, Y1 - 2006/08/22/ PY - 2005/05/26/received PY - 2005/10/13/accepted PY - 2006/8/24/pubmed PY - 2006/10/25/medline PY - 2006/8/24/entrez SP - 1557 EP - 66 JF - Digestive diseases and sciences JO - Dig Dis Sci VL - 51 IS - 9 N2 - Glucagon-like peptide-2 (GLP-2) is an enteroendocrine hormone which is uniquely trophic for the intestine; a physiological role in regulating nutrient absorptive capacity is becoming apparent. GLP-2, independent of enteral feeding, stimulates a classical pattern of intestinal adaptation in terminal ileum following resection. Herein we investigate the effects of GLP-2 on the jejunal remant using a rat model of short bowel syndrome (SBS). Juvenile 250- to 275-g SD rats underwent 80% distal small bowel resection, leaving 20 cm of proximal jejunum and venous catheterization. Animals were maintained with total parenteral nutrition (TPN) or TPN+10 microg/kg/hr GLP-2 (n=8 per group). After 7 days, intestinal permeability was assessed by urinary recovery of gavaged carbohydrate probes. Animals were euthanized, and the intestines taken for analysis of morphology, crypt cell proliferation, apoptosis, and expression of SGLT-1 and GLUT-5 transport proteins. GLP-2 treatment reduced intestinal permeability and increased in vivo glucose absorption, small intestinal weight, surface area, villus height, crypt depth, and microvillus height. Intestinal mucosal DNA and protein content per unit length of the small bowel were increased (P < 0.05 for all comparisons). However, in contrast to previous studies examining GLP-2's effects on remnant ileum, the jejunal crypt apoptotic index was increased in GLP-2-treated animals, with no increase in SGLT-1 or GLUT 5 expression. These results show that exogenous GLP-2 treatment of animals with jejunal remnant reduces intestinal permeability, increases glucose absorption, and stimulates morphological features of intestinal adaptation including increased micovillus height and surface area. However, the pattern of changes seen is different from that in remnant ileum. This suggests that GLP-2's effects are specific to different regions of the bowel. Nonetheless, remnant jejunum is responsive to GLP-2 in the absence of enteral nutrition. Further studies are warranted to establish the mechanisms of action and therapeutic potential of GLP-2 in modulating nutrient absorptive capacity. SN - 0163-2116 UR - https://www.unboundmedicine.com/medline/citation/16927140/Glucagon_like_peptide_2_induces_a_specific_pattern_of_adaptation_in_remnant_jejunum_ DB - PRIME DP - Unbound Medicine ER -