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Effects of exogenous glucagon-like peptide-2 and distal bowel resection on intestinal and systemic adaptive responses in rats.
PLoS One. 2017; 12(7):e0181453.Plos

Abstract

OBJECTIVE

To determine the effects of exogenous glucagon-like peptide-2 (GLP-2), with or without massive distal bowel resection, on adaptation of jejunal mucosa, enteric neurons, gut hormones and tissue reserves in rats.

BACKGROUND

GLP-2 is a gut hormone known to be trophic for small bowel mucosa, and to mimic intestinal adaptation in short bowel syndrome (SBS). However, the effects of exogenous GLP-2 and SBS on enteric neurons are unclear.

METHODS

Sprague Dawley rats were randomized to four treatments: Transected Bowel (TB) (n = 8), TB + GLP-2 (2.5 nmol/kg/h, n = 8), SBS (n = 5), or SBS + GLP-2 (2.5 nmol/kg/h, n = 9). SBS groups underwent a 60% jejunoileal resection with cecectomy and jejunocolic anastomosis. All rats were maintained on parenteral nutrition for 7 d. Parameters measured included gut morphometry, qPCR for hexose transporter (SGLT-1, GLUT-2, GLUT-5) and GLP-2 receptor mRNA, whole mount immunohistochemistry for neurons (HuC/D, VIP, nNOS), plasma glucose, gut hormones, and body composition.

RESULTS

Resection increased the proportion of nNOS immunopositive myenteric neurons, intestinal muscularis propria thickness and crypt cell proliferation, which were not recapitulated by GLP-2 therapy. Exogenous GLP-2 increased jejunal mucosal surface area without affecting enteric VIP or nNOS neuronal immunopositivity, attenuated resection-induced reductions in jejunal hexose transporter abundance (SGLT-1, GLUT-2), increased plasma amylin and decreased peptide YY concentrations. Exogenous GLP-2 attenuated resection-induced increases in blood glucose and body fat loss.

CONCLUSIONS

Exogenous GLP-2 stimulates jejunal adaptation independent of enteric neuronal VIP or nNOS changes, and has divergent effects on plasma amylin and peptide YY concentrations. The novel ability of exogenous GLP-2 to modulate resection-induced changes in peripheral glucose and lipid reserves may be important in understanding the whole-body response following intestinal resection, and is worthy of further study.

Links

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Authors+Show Affiliations

Lai SW
Department of Surgery, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
de Heuvel E
Department of Surgery, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Wallace LE
Department of Surgery, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Hartmann B
Department of Biomedical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, The Panum Institute, Copenhagen, Denmark.
Holst JJ
Department of Biomedical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, The Panum Institute, Copenhagen, Denmark.
Brindle ME
Department of Surgery, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Chelikani PK
Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.
Sigalet DL
Department of Surgery, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. Department of Surgery, Sidra Medical and Research Center and Weil Cornell Medical College, Doha, Qatar.

MeSH

Adaptation, PhysiologicalAnimalsDigestive System Surgical ProceduresDisease Models, AnimalGlucagon-Like Peptide 2Intestinal MucosaJejunumMaleParenteral NutritionParenteral Nutrition, TotalRatsRats, Sprague-DawleyShort Bowel Syndrome

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28738080

Citation

Lai, Sarah W., et al. "Effects of Exogenous Glucagon-like Peptide-2 and Distal Bowel Resection On Intestinal and Systemic Adaptive Responses in Rats." PloS One, vol. 12, no. 7, 2017, pp. e0181453.
Lai SW, de Heuvel E, Wallace LE, et al. Effects of exogenous glucagon-like peptide-2 and distal bowel resection on intestinal and systemic adaptive responses in rats. PLoS One. 2017;12(7):e0181453.
Lai, S. W., de Heuvel, E., Wallace, L. E., Hartmann, B., Holst, J. J., Brindle, M. E., Chelikani, P. K., & Sigalet, D. L. (2017). Effects of exogenous glucagon-like peptide-2 and distal bowel resection on intestinal and systemic adaptive responses in rats. PloS One, 12(7), e0181453. https://doi.org/10.1371/journal.pone.0181453
Lai SW, et al. Effects of Exogenous Glucagon-like Peptide-2 and Distal Bowel Resection On Intestinal and Systemic Adaptive Responses in Rats. PLoS One. 2017;12(7):e0181453. PubMed PMID: 28738080.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of exogenous glucagon-like peptide-2 and distal bowel resection on intestinal and systemic adaptive responses in rats. AU - Lai,Sarah W, AU - de Heuvel,Elaine, AU - Wallace,Laurie E, AU - Hartmann,Bolette, AU - Holst,Jens J, AU - Brindle,Mary E, AU - Chelikani,Prasanth K, AU - Sigalet,David L, Y1 - 2017/07/24/ PY - 2017/02/04/received PY - 2017/07/01/accepted PY - 2017/7/25/entrez PY - 2017/7/25/pubmed PY - 2017/9/22/medline SP - e0181453 EP - e0181453 JF - PloS one JO - PLoS One VL - 12 IS - 7 N2 - OBJECTIVE: To determine the effects of exogenous glucagon-like peptide-2 (GLP-2), with or without massive distal bowel resection, on adaptation of jejunal mucosa, enteric neurons, gut hormones and tissue reserves in rats. BACKGROUND: GLP-2 is a gut hormone known to be trophic for small bowel mucosa, and to mimic intestinal adaptation in short bowel syndrome (SBS). However, the effects of exogenous GLP-2 and SBS on enteric neurons are unclear. METHODS: Sprague Dawley rats were randomized to four treatments: Transected Bowel (TB) (n = 8), TB + GLP-2 (2.5 nmol/kg/h, n = 8), SBS (n = 5), or SBS + GLP-2 (2.5 nmol/kg/h, n = 9). SBS groups underwent a 60% jejunoileal resection with cecectomy and jejunocolic anastomosis. All rats were maintained on parenteral nutrition for 7 d. Parameters measured included gut morphometry, qPCR for hexose transporter (SGLT-1, GLUT-2, GLUT-5) and GLP-2 receptor mRNA, whole mount immunohistochemistry for neurons (HuC/D, VIP, nNOS), plasma glucose, gut hormones, and body composition. RESULTS: Resection increased the proportion of nNOS immunopositive myenteric neurons, intestinal muscularis propria thickness and crypt cell proliferation, which were not recapitulated by GLP-2 therapy. Exogenous GLP-2 increased jejunal mucosal surface area without affecting enteric VIP or nNOS neuronal immunopositivity, attenuated resection-induced reductions in jejunal hexose transporter abundance (SGLT-1, GLUT-2), increased plasma amylin and decreased peptide YY concentrations. Exogenous GLP-2 attenuated resection-induced increases in blood glucose and body fat loss. CONCLUSIONS: Exogenous GLP-2 stimulates jejunal adaptation independent of enteric neuronal VIP or nNOS changes, and has divergent effects on plasma amylin and peptide YY concentrations. The novel ability of exogenous GLP-2 to modulate resection-induced changes in peripheral glucose and lipid reserves may be important in understanding the whole-body response following intestinal resection, and is worthy of further study. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/28738080/Effects_of_exogenous_glucagon_like_peptide_2_and_distal_bowel_resection_on_intestinal_and_systemic_adaptive_responses_in_rats_ DB - PRIME DP - Unbound Medicine ER -