Differential Effects on Intestinal Adaptation Following Exogenous Glucagon-Like Peptide 2 Therapy with and Without Enteral Nutrition in Neonatal Short Bowel Syndrome

David W. Lim, Abdoulaye Diane, Mitsuru Muto, Donna F. Vine, Patrick N. Nation, Pamela R. Wizzard, David L. Sigalet, David L. Bigam, Paul B. Pencharz, Justine M. Turner, Paul W. Wales

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)156-170
Number of pages15
JournalJournal of Parenteral and Enteral Nutrition
Volume41
Issue number2
DOIs
Publication statusPublished - 1 Jan 2017
Externally publishedYes

Fingerprint

Glucagon-Like Peptide 2
Short Bowel Syndrome
Enteral Nutrition
Ileum
Anatomy
Therapeutics
Analysis of Variance
Fats
Food
Parenteral Nutrition
Intestines
Proteins
Clinical Trials
Weights and Measures
Polymerase Chain Reaction
Messenger RNA

Keywords

  • enteral nutrition
  • glucagon-like peptide 2
  • intestinal adaptation
  • intestinal failure
  • neonatal
  • piglet model
  • short bowel syndrome

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Differential Effects on Intestinal Adaptation Following Exogenous Glucagon-Like Peptide 2 Therapy with and Without Enteral Nutrition in Neonatal Short Bowel Syndrome. / Lim, David W.; Diane, Abdoulaye; Muto, Mitsuru; Vine, Donna F.; Nation, Patrick N.; Wizzard, Pamela R.; Sigalet, David L.; Bigam, David L.; Pencharz, Paul B.; Turner, Justine M.; Wales, Paul W.

In: Journal of Parenteral and Enteral Nutrition, Vol. 41, No. 2, 01.01.2017, p. 156-170.

Research output: Contribution to journalArticle

Lim, David W. ; Diane, Abdoulaye ; Muto, Mitsuru ; Vine, Donna F. ; Nation, Patrick N. ; Wizzard, Pamela R. ; Sigalet, David L. ; Bigam, David L. ; Pencharz, Paul B. ; Turner, Justine M. ; Wales, Paul W. / Differential Effects on Intestinal Adaptation Following Exogenous Glucagon-Like Peptide 2 Therapy with and Without Enteral Nutrition in Neonatal Short Bowel Syndrome. In: Journal of Parenteral and Enteral Nutrition. 2017 ; Vol. 41, No. 2. pp. 156-170.
@article{cce7f686f07a4100a2c34887a24deb5c,
title = "Differential Effects on Intestinal Adaptation Following Exogenous Glucagon-Like Peptide 2 Therapy with and Without Enteral Nutrition in Neonatal Short Bowel Syndrome",
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.",
keywords = "enteral nutrition, glucagon-like peptide 2, intestinal adaptation, intestinal failure, neonatal, piglet model, short bowel syndrome",
author = "Lim, {David W.} and Abdoulaye Diane and Mitsuru Muto and Vine, {Donna F.} and Nation, {Patrick N.} and Wizzard, {Pamela R.} and Sigalet, {David L.} and Bigam, {David L.} and Pencharz, {Paul B.} and Turner, {Justine M.} and Wales, {Paul W.}",
year = "2017",
month = "1",
day = "1",
doi = "10.1177/0148607116665812",
language = "English",
volume = "41",
pages = "156--170",
journal = "Journal of Parenteral and Enteral Nutrition",
issn = "0148-6071",
publisher = "SAGE Publications Inc.",
number = "2",

}

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

AU - Lim, David W.

AU - Diane, 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.

PY - 2017/1/1

Y1 - 2017/1/1

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.

AB - 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.

KW - enteral nutrition

KW - glucagon-like peptide 2

KW - intestinal adaptation

KW - intestinal failure

KW - neonatal

KW - piglet model

KW - short bowel syndrome

UR - http://www.scopus.com/inward/record.url?scp=85011596061&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85011596061&partnerID=8YFLogxK

U2 - 10.1177/0148607116665812

DO - 10.1177/0148607116665812

M3 - Article

VL - 41

SP - 156

EP - 170

JO - Journal of Parenteral and Enteral Nutrition

JF - Journal of Parenteral and Enteral Nutrition

SN - 0148-6071

IS - 2

ER -