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Exogenous glucagon-like peptide-2 (GLP-2) augments GLP-2 receptor mRNA and maintains proglucagon mRNA levels in resected rats.
JPEN J Parenter Enteral Nutr. 2008 May-Jun; 32(3):254-65.JJ

Abstract

BACKGROUND

Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent proglucagon-derived hormone that stimulates intestinal adaptive growth. Our aim was 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 microg/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). Ileal 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 was 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.

Authors+Show Affiliations

Department of Nutritional Sciences, University of Wisconsin, Madison, WI, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

18443137

Citation

Koopmann, Matthew C., et al. "Exogenous Glucagon-like Peptide-2 (GLP-2) Augments GLP-2 Receptor mRNA and Maintains Proglucagon mRNA Levels in Resected Rats." JPEN. Journal of Parenteral and Enteral Nutrition, vol. 32, no. 3, 2008, pp. 254-65.
Koopmann MC, Nelson DW, Murali SG, et al. Exogenous glucagon-like peptide-2 (GLP-2) augments GLP-2 receptor mRNA and maintains proglucagon mRNA levels in resected rats. JPEN J Parenter Enteral Nutr. 2008;32(3):254-65.
Koopmann, M. C., Nelson, D. W., Murali, S. G., Liu, X., Brownfield, M. S., Holst, J. J., & Ney, D. M. (2008). Exogenous glucagon-like peptide-2 (GLP-2) augments GLP-2 receptor mRNA and maintains proglucagon mRNA levels in resected rats. JPEN. Journal of Parenteral and Enteral Nutrition, 32(3), 254-65. https://doi.org/10.1177/0148607108316198
Koopmann MC, et al. Exogenous Glucagon-like Peptide-2 (GLP-2) Augments GLP-2 Receptor mRNA and Maintains Proglucagon mRNA Levels in Resected Rats. JPEN J Parenter Enteral Nutr. 2008 May-Jun;32(3):254-65. PubMed PMID: 18443137.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exogenous glucagon-like peptide-2 (GLP-2) augments GLP-2 receptor mRNA and maintains proglucagon mRNA levels in resected rats. AU - Koopmann,Matthew C, AU - Nelson,David W, AU - Murali,Sangita G, AU - Liu,Xiaowen, AU - Brownfield,Mark S, AU - Holst,Jens J, AU - Ney,Denise M, PY - 2008/4/30/pubmed PY - 2008/8/12/medline PY - 2008/4/30/entrez SP - 254 EP - 65 JF - JPEN. Journal of parenteral and enteral nutrition JO - JPEN J Parenter Enteral Nutr VL - 32 IS - 3 N2 - BACKGROUND: Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent proglucagon-derived hormone that stimulates intestinal adaptive growth. Our aim was 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 microg/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). Ileal 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 was 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. SN - 0148-6071 UR - https://www.unboundmedicine.com/medline/citation/18443137/Exogenous_glucagon_like_peptide_2__GLP_2__augments_GLP_2_receptor_mRNA_and_maintains_proglucagon_mRNA_levels_in_resected_rats_ DB - PRIME DP - Unbound Medicine ER -