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Sustained glucagon-like peptide-2 infusion is required for intestinal adaptation, and cessation reverses increased cellularity in rats with intestinal failure.
Am J Physiol Gastrointest Liver Physiol. 2010 Dec; 299(6):G1222-30.AJ

Abstract

Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived hormone that is a proposed treatment for human short bowel syndrome (SBS). The objective was to determine how the timing, duration, and cessation of GLP-2 administration affect intestinal adaptation and enterocyte kinetics in a rat model of human SBS that results in intestinal failure requiring total parenteral nutrition (TPN). Rats underwent 60% jejunoileal resection plus cecectomy and jugular vein cannulation and were maintained exclusively with TPN for 18 days in these treatments: TPN control (no GLP-2); sustained GLP-2 (1-18 days); early GLP-2 (1-7 days, killed at 7 or 18 days); and delayed GLP-2 (12-18 days). Body weight gain was similar across groups, and plasma bioactive GLP-2 was significantly increased with coinfusion of GLP-2 (100 μg·kg⁻¹·day⁻¹) with TPN. GLP-2-treated rats showed significant increases in duodenum and jejunum mucosal dry mass, protein, DNA, and sucrase activity compared with TPN control. The increased jejunum cellularity reflected significantly decreased apoptosis and increased crypt mitosis and crypt fission due to GLP-2. When GLP-2 infusion stopped at 7 days, these effects were reversed at 18 days. Sustained GLP-2 infusion significantly increased duodenum length and decreased 18-day mortality to 0% from 37.5% deaths in TPN control (P = 0.08). Colon proglucagon expression quantified by real-time RT-qPCR was increased in TPN controls and attenuated by GLP-2 infusion; jejunal expression of the GLP-2 receptor did not differ among groups. In summary, early, sustained GLP-2 infusion reduces mortality, induces crypt fission, and is required for intestinal adaptation, whereas cessation of GLP-2 reverses gains in mucosal cellularity in a rat model of intestinal failure.

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Authors+Show Affiliations

Koopmann MC
Department of Nutritional Sciences, Univ. of Wisconsin-Madison, 53706, USA.
Chen X
No affiliation info available
Holst JJ
No affiliation info available
Ney DM
No affiliation info available

MeSH

AnimalsApoptosisBody WeightDrug Administration ScheduleEnterocytesGene Expression RegulationGlucagon-Like Peptide 2Intestine, SmallMaleMitosisParenteral Nutrition, TotalProglucagonRatsRats, Sprague-DawleyShort Bowel Syndrome

Pub Type(s)

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

Language

eng

PubMed ID

20864657

Citation

Koopmann, Matthew C., et al. "Sustained Glucagon-like Peptide-2 Infusion Is Required for Intestinal Adaptation, and Cessation Reverses Increased Cellularity in Rats With Intestinal Failure." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 299, no. 6, 2010, pp. G1222-30.
Koopmann MC, Chen X, Holst JJ, et al. Sustained glucagon-like peptide-2 infusion is required for intestinal adaptation, and cessation reverses increased cellularity in rats with intestinal failure. Am J Physiol Gastrointest Liver Physiol. 2010;299(6):G1222-30.
Koopmann, M. C., Chen, X., Holst, J. J., & Ney, D. M. (2010). Sustained glucagon-like peptide-2 infusion is required for intestinal adaptation, and cessation reverses increased cellularity in rats with intestinal failure. American Journal of Physiology. Gastrointestinal and Liver Physiology, 299(6), G1222-30. https://doi.org/10.1152/ajpgi.00367.2010
Koopmann MC, et al. Sustained Glucagon-like Peptide-2 Infusion Is Required for Intestinal Adaptation, and Cessation Reverses Increased Cellularity in Rats With Intestinal Failure. Am J Physiol Gastrointest Liver Physiol. 2010;299(6):G1222-30. PubMed PMID: 20864657.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sustained glucagon-like peptide-2 infusion is required for intestinal adaptation, and cessation reverses increased cellularity in rats with intestinal failure. AU - Koopmann,Matthew C, AU - Chen,Xueyan, AU - Holst,Jens J, AU - Ney,Denise M, Y1 - 2010/09/23/ PY - 2010/9/25/entrez PY - 2010/9/25/pubmed PY - 2011/1/19/medline SP - G1222 EP - 30 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 299 IS - 6 N2 - Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived hormone that is a proposed treatment for human short bowel syndrome (SBS). The objective was to determine how the timing, duration, and cessation of GLP-2 administration affect intestinal adaptation and enterocyte kinetics in a rat model of human SBS that results in intestinal failure requiring total parenteral nutrition (TPN). Rats underwent 60% jejunoileal resection plus cecectomy and jugular vein cannulation and were maintained exclusively with TPN for 18 days in these treatments: TPN control (no GLP-2); sustained GLP-2 (1-18 days); early GLP-2 (1-7 days, killed at 7 or 18 days); and delayed GLP-2 (12-18 days). Body weight gain was similar across groups, and plasma bioactive GLP-2 was significantly increased with coinfusion of GLP-2 (100 μg·kg⁻¹·day⁻¹) with TPN. GLP-2-treated rats showed significant increases in duodenum and jejunum mucosal dry mass, protein, DNA, and sucrase activity compared with TPN control. The increased jejunum cellularity reflected significantly decreased apoptosis and increased crypt mitosis and crypt fission due to GLP-2. When GLP-2 infusion stopped at 7 days, these effects were reversed at 18 days. Sustained GLP-2 infusion significantly increased duodenum length and decreased 18-day mortality to 0% from 37.5% deaths in TPN control (P = 0.08). Colon proglucagon expression quantified by real-time RT-qPCR was increased in TPN controls and attenuated by GLP-2 infusion; jejunal expression of the GLP-2 receptor did not differ among groups. In summary, early, sustained GLP-2 infusion reduces mortality, induces crypt fission, and is required for intestinal adaptation, whereas cessation of GLP-2 reverses gains in mucosal cellularity in a rat model of intestinal failure. SN - 1522-1547 UR - https://www.unboundmedicine.com/medline/citation/20864657/Sustained_glucagon_like_peptide_2_infusion_is_required_for_intestinal_adaptation_and_cessation_reverses_increased_cellularity_in_rats_with_intestinal_failure_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00367.2010?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -