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Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure.
Am J Physiol Gastrointest Liver Physiol. 2012 Sep 01; 303(5):G610-22.AJ

Abstract

Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that shows promise for the treatment of short bowel syndrome (SBS). Our objective was to investigate how combination GLP-2 + enteral nutrients (EN) affects intestinal adaption in a rat model that mimics severe human SBS and requires parenteral nutrition (PN). Male Sprague-Dawley rats were assigned to one of five groups and maintained with PN for 18 days: total parenteral nutrition (TPN) alone, TPN + GLP-2 (100 μg·kg(-1)·day(-1)), PN + EN + GLP-2(7 days), PN + EN + GLP-2(18 days), and a nonsurgical oral reference group. Animals underwent massive distal bowel resection followed by jejunocolic anastomosis and placement of jugular catheters. Starting on postoperative day 4, rats in the EN groups were allowed ad libitum access to EN. Groups provided PN + EN + GLP-2 had their rate of PN reduced by 0.25 ml/day starting on postoperative day 6. Groups provided PN + EN + GLP-2 demonstrated significantly greater body weight gain with similar energy intake and a safe 80% reduction in PN compared with TPN ± GLP-2. Groups provided PN + EN + GLP-2 for 7 or 18 days showed similar body weight gain, residual jejunal length, and digestive capacity. Groups provided PN + EN + GLP-2 showed increased jejunal GLP-2 receptor (GLP-2R), insulin-like growth factor-I (IGF-I), and IGF-binding protein-5 (IGFBP-5) expression. Treatment with TPN + GLP-2 demonstrated increased jejunal expression of epidermal growth factor. Cessation of GLP-2 after 7 days with continued EN sustained the majority of intestinal adaption and significantly increased expression of colonic proglucagon compared with PN + EN + GLP-2 for 18 days, and increased plasma GLP-2 concentrations compared with TPN alone. In summary, EN potentiate the intestinotrophic actions of GLP-2 by improving body weight gain allowing for a safe 80% reduction in PN with increased jejunal expression of GLP-2R, IGF-I, and IGFBP-5 following distal bowel resection in the rat.

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Authors+Show Affiliations

Brinkman AS
Department of Surgery, University of Wisconsin-Madison, USA.
Murali SG
No affiliation info available
Hitt S
No affiliation info available
Solverson PM
No affiliation info available
Holst JJ
No affiliation info available
Ney DM
No affiliation info available

MeSH

AnimalsDisease Models, AnimalEnteral NutritionGlucagon-Like Peptide 2HumansInsulin-Like Growth Factor IIntestine, SmallMaleMitotic IndexParenteral NutritionProglucagonRatsRats, Sprague-DawleyReal-Time Polymerase Chain ReactionShort Bowel Syndrome

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22744334

Citation

Brinkman, Adam S., et al. "Enteral Nutrients Potentiate Glucagon-like Peptide-2 Action and Reduce Dependence On Parenteral Nutrition in a Rat Model of Human Intestinal Failure." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 303, no. 5, 2012, pp. G610-22.
Brinkman AS, Murali SG, Hitt S, et al. Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure. Am J Physiol Gastrointest Liver Physiol. 2012;303(5):G610-22.
Brinkman, A. S., Murali, S. G., Hitt, S., Solverson, P. M., Holst, J. J., & Ney, D. M. (2012). Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure. American Journal of Physiology. Gastrointestinal and Liver Physiology, 303(5), G610-22. https://doi.org/10.1152/ajpgi.00184.2012
Brinkman AS, et al. Enteral Nutrients Potentiate Glucagon-like Peptide-2 Action and Reduce Dependence On Parenteral Nutrition in a Rat Model of Human Intestinal Failure. Am J Physiol Gastrointest Liver Physiol. 2012 Sep 1;303(5):G610-22. PubMed PMID: 22744334.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure. AU - Brinkman,Adam S, AU - Murali,Sangita G, AU - Hitt,Stacy, AU - Solverson,Patrick M, AU - Holst,Jens J, AU - Ney,Denise M, Y1 - 2012/06/28/ PY - 2012/6/30/entrez PY - 2012/6/30/pubmed PY - 2012/12/12/medline SP - G610 EP - 22 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 303 IS - 5 N2 - Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that shows promise for the treatment of short bowel syndrome (SBS). Our objective was to investigate how combination GLP-2 + enteral nutrients (EN) affects intestinal adaption in a rat model that mimics severe human SBS and requires parenteral nutrition (PN). Male Sprague-Dawley rats were assigned to one of five groups and maintained with PN for 18 days: total parenteral nutrition (TPN) alone, TPN + GLP-2 (100 μg·kg(-1)·day(-1)), PN + EN + GLP-2(7 days), PN + EN + GLP-2(18 days), and a nonsurgical oral reference group. Animals underwent massive distal bowel resection followed by jejunocolic anastomosis and placement of jugular catheters. Starting on postoperative day 4, rats in the EN groups were allowed ad libitum access to EN. Groups provided PN + EN + GLP-2 had their rate of PN reduced by 0.25 ml/day starting on postoperative day 6. Groups provided PN + EN + GLP-2 demonstrated significantly greater body weight gain with similar energy intake and a safe 80% reduction in PN compared with TPN ± GLP-2. Groups provided PN + EN + GLP-2 for 7 or 18 days showed similar body weight gain, residual jejunal length, and digestive capacity. Groups provided PN + EN + GLP-2 showed increased jejunal GLP-2 receptor (GLP-2R), insulin-like growth factor-I (IGF-I), and IGF-binding protein-5 (IGFBP-5) expression. Treatment with TPN + GLP-2 demonstrated increased jejunal expression of epidermal growth factor. Cessation of GLP-2 after 7 days with continued EN sustained the majority of intestinal adaption and significantly increased expression of colonic proglucagon compared with PN + EN + GLP-2 for 18 days, and increased plasma GLP-2 concentrations compared with TPN alone. In summary, EN potentiate the intestinotrophic actions of GLP-2 by improving body weight gain allowing for a safe 80% reduction in PN with increased jejunal expression of GLP-2R, IGF-I, and IGFBP-5 following distal bowel resection in the rat. SN - 1522-1547 UR - https://www.unboundmedicine.com/medline/citation/22744334/Enteral_nutrients_potentiate_glucagon_like_peptide_2_action_and_reduce_dependence_on_parenteral_nutrition_in_a_rat_model_of_human_intestinal_failure_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00184.2012?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -