Tags

Type your tag names separated by a space and hit enter

Differential Effects on Intestinal Adaptation Following Exogenous Glucagon-Like Peptide 2 Therapy With and Without Enteral Nutrition in Neonatal Short Bowel Syndrome [Formula: see text].
JPEN J Parenter Enteral Nutr. 2017 02; 41(2):156-170.JJ

Abstract

BACKGROUND

We aim to study the efficacy of exogenously administered glucagon-like peptide 2 (GLP-2) on intestinal adaptation in 2 preclinical models of neonatal short bowel syndrome (SBS) according to remnant intestinal anatomy, with and without ileum. Furthermore, we aim to determine if this adaptive effect was potentiated with enteral nutrition (EN).

METHODS

Neonatal piglets were block-randomized to 75% mid-intestinal (JI group, retains ileum) or distal-intestinal (JC group, has no ileum) resection or no resection (sham control) and GLP-2 treatment (11 nmol/kg/d) or saline control for 7 days. Piglets received nutrition support, either 100% parenteral nutrition (PN; 0% EN, n = 32 in total) or 80% PN + 40% EN (n = 28 in total). Adaptation was assessed by morphological and histological changes, as well as RT quantitative polymerase chain reaction of nutrient transporters and tight junctional proteins and fat absorption. Data are analyzed by 3-way analysis of variance (ANOVA) and 2-way ANOVA per EN level.

RESULTS

GLP-2 treatment lengthened villi, deepened crypts, and improved intestinal weight in the remnant intestine of JC piglets. EN was a more potent adaptive stimulus for JI piglets. Small intestinal lengthening occurred only in the JI group, when given EN. There was no difference in total fat absorption and messenger RNA expression of nutrient transporters and tight junctional proteins.

CONCLUSIONS

GLP-2 administration augmented structural adaptation in JC piglets with distal intestinal resection. Given JI anatomy, further stimulation by GLP-2 treatment over innate adaptation and stimulation by EN was modest and restricted to ileum. The differential effect of GLP-2 in neonatal SBS, depending on remnant anatomy, has important implications for clinical translation and planning of clinical trials.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Lim DW
1 Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
Diané A
2 Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
Muto M
3 Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Vine DF
2 Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
Nation PN
4 Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
Wizzard PR
3 Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Sigalet DL
5 Department of Surgery, University of Calgary, Calgary, Alberta, Canada.
Bigam DL
1 Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
Pencharz PB
6 Department of Nutritional Sciences and Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
Turner JM
2 Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada. 3 Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Wales PW
1 Department of Surgery, University of Alberta, Edmonton, Alberta, Canada. 3 Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada. 7 Department of Surgery, Hospital for Sick Children & University of Toronto, Toronto, Ontario, Canada.

MeSH

Adaptation, PhysiologicalAnimalsAnimals, NewbornDietary FatsDisease Models, AnimalEnteral NutritionGlucagon-Like Peptide 2HumansIntestinal AbsorptionIntestinesMaleParenteral NutritionShort Bowel SyndromeSus scrofa

Pub Type(s)

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

Language

eng

PubMed ID

27660290

Citation

Lim, David W., et al. "Differential Effects On Intestinal Adaptation Following Exogenous Glucagon-Like Peptide 2 Therapy With and Without Enteral Nutrition in Neonatal Short Bowel Syndrome [Formula: See Text]." JPEN. Journal of Parenteral and Enteral Nutrition, vol. 41, no. 2, 2017, pp. 156-170.
Lim DW, Diané A, Muto M, et al. Differential Effects on Intestinal Adaptation Following Exogenous Glucagon-Like Peptide 2 Therapy With and Without Enteral Nutrition in Neonatal Short Bowel Syndrome [Formula: see text]. JPEN J Parenter Enteral Nutr. 2017;41(2):156-170.
Lim, D. W., Diané, A., Muto, M., Vine, D. F., Nation, P. N., Wizzard, P. R., Sigalet, D. L., Bigam, D. L., Pencharz, P. B., Turner, J. M., & Wales, P. W. (2017). Differential Effects on Intestinal Adaptation Following Exogenous Glucagon-Like Peptide 2 Therapy With and Without Enteral Nutrition in Neonatal Short Bowel Syndrome [Formula: see text]. JPEN. Journal of Parenteral and Enteral Nutrition, 41(2), 156-170. https://doi.org/10.1177/0148607116665812
Lim DW, et al. Differential Effects On Intestinal Adaptation Following Exogenous Glucagon-Like Peptide 2 Therapy With and Without Enteral Nutrition in Neonatal Short Bowel Syndrome [Formula: See Text]. JPEN J Parenter Enteral Nutr. 2017;41(2):156-170. PubMed PMID: 27660290.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential Effects on Intestinal Adaptation Following Exogenous Glucagon-Like Peptide 2 Therapy With and Without Enteral Nutrition in Neonatal Short Bowel Syndrome [Formula: see text]. AU - Lim,David W, AU - Diané,Abdoulaye, AU - Muto,Mitsuru, AU - Vine,Donna F, AU - Nation,Patrick N, AU - Wizzard,Pamela R, AU - Sigalet,David L, AU - Bigam,David L, AU - Pencharz,Paul B, AU - Turner,Justine M, AU - Wales,Paul W, Y1 - 2016/09/28/ PY - 2016/9/24/pubmed PY - 2017/12/2/medline PY - 2016/9/24/entrez KW - enteral nutrition KW - glucagon-like peptide 2 KW - intestinal adaptation KW - intestinal failure KW - neonatal KW - piglet model KW - short bowel syndrome SP - 156 EP - 170 JF - JPEN. Journal of parenteral and enteral nutrition JO - JPEN J Parenter Enteral Nutr VL - 41 IS - 2 N2 - BACKGROUND: We aim to study the efficacy of exogenously administered glucagon-like peptide 2 (GLP-2) on intestinal adaptation in 2 preclinical models of neonatal short bowel syndrome (SBS) according to remnant intestinal anatomy, with and without ileum. Furthermore, we aim to determine if this adaptive effect was potentiated with enteral nutrition (EN). METHODS: Neonatal piglets were block-randomized to 75% mid-intestinal (JI group, retains ileum) or distal-intestinal (JC group, has no ileum) resection or no resection (sham control) and GLP-2 treatment (11 nmol/kg/d) or saline control for 7 days. Piglets received nutrition support, either 100% parenteral nutrition (PN; 0% EN, n = 32 in total) or 80% PN + 40% EN (n = 28 in total). Adaptation was assessed by morphological and histological changes, as well as RT quantitative polymerase chain reaction of nutrient transporters and tight junctional proteins and fat absorption. Data are analyzed by 3-way analysis of variance (ANOVA) and 2-way ANOVA per EN level. RESULTS: GLP-2 treatment lengthened villi, deepened crypts, and improved intestinal weight in the remnant intestine of JC piglets. EN was a more potent adaptive stimulus for JI piglets. Small intestinal lengthening occurred only in the JI group, when given EN. There was no difference in total fat absorption and messenger RNA expression of nutrient transporters and tight junctional proteins. CONCLUSIONS: GLP-2 administration augmented structural adaptation in JC piglets with distal intestinal resection. Given JI anatomy, further stimulation by GLP-2 treatment over innate adaptation and stimulation by EN was modest and restricted to ileum. The differential effect of GLP-2 in neonatal SBS, depending on remnant anatomy, has important implications for clinical translation and planning of clinical trials. SN - 1941-2444 UR - https://www.unboundmedicine.com/medline/citation/27660290/Differential_Effects_on_Intestinal_Adaptation_Following_Exogenous_Glucagon_Like_Peptide_2_Therapy_With_and_Without_Enteral_Nutrition_in_Neonatal_Short_Bowel_Syndrome_[Formula:_see_text]_ DB - PRIME DP - Unbound Medicine ER -