Exogenous glucagon-like peptide-2 (GLP-2) augments GLP-2 receptor mRNA and maintains proglucagon mRNA levels in resected rats

Matthew Koopman, David W. Nelson, Sangita G. Murali, Liu Xiaowen Liu, Mark S. Brownfield, Jens J. Holst, Denise M. Ney

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 μg/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.

Original languageEnglish (US)
Pages (from-to)254-265
Number of pages12
JournalJournal of Parenteral and Enteral Nutrition
Volume32
Issue number3
DOIs
StatePublished - May 1 2008
Externally publishedYes

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Glucagon-Like Peptide 2
Proglucagon
Messenger RNA
Ileum
Jejunum
Glucagon-Like Peptide-2 Receptor
Body Weight
Enteroendocrine Cells
Gastrointestinal Hormones
Sucrase
Enterocytes
Nitric Oxide Synthase Type III
Vasoactive Intestinal Peptide
Bromodeoxyuridine
Growth
Reverse Transcriptase Polymerase Chain Reaction
Duodenum
Northern Blotting

Keywords

  • Bowel resection
  • GI hormones
  • Intestinal adaptation
  • Intestinal failure
  • Short bowel syndrome

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Exogenous glucagon-like peptide-2 (GLP-2) augments GLP-2 receptor mRNA and maintains proglucagon mRNA levels in resected rats. / Koopman, Matthew; Nelson, David W.; Murali, Sangita G.; Xiaowen Liu, Liu; Brownfield, Mark S.; Holst, Jens J.; Ney, Denise M.

In: Journal of Parenteral and Enteral Nutrition, Vol. 32, No. 3, 01.05.2008, p. 254-265.

Research output: Contribution to journalArticle

Koopman, Matthew ; Nelson, David W. ; Murali, Sangita G. ; Xiaowen Liu, Liu ; Brownfield, Mark S. ; Holst, Jens J. ; Ney, Denise M. / Exogenous glucagon-like peptide-2 (GLP-2) augments GLP-2 receptor mRNA and maintains proglucagon mRNA levels in resected rats. In: Journal of Parenteral and Enteral Nutrition. 2008 ; Vol. 32, No. 3. pp. 254-265.
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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 μg/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.",
keywords = "Bowel resection, GI hormones, Intestinal adaptation, Intestinal failure, Short bowel syndrome",
author = "Matthew Koopman and Nelson, {David W.} and Murali, {Sangita G.} and {Xiaowen Liu}, Liu and Brownfield, {Mark S.} and Holst, {Jens J.} and Ney, {Denise M.}",
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AU - Koopman, Matthew

AU - Nelson, David W.

AU - Murali, Sangita G.

AU - Xiaowen Liu, Liu

AU - Brownfield, Mark S.

AU - Holst, Jens J.

AU - Ney, Denise M.

PY - 2008/5/1

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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 μg/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.

AB - 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 μg/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.

KW - Bowel resection

KW - GI hormones

KW - Intestinal adaptation

KW - Intestinal failure

KW - Short bowel syndrome

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