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

JPEN J Parenter Enteral Nutr. May-Jun 2008;32(3):254-65. doi: 10.1177/0148607108316198.

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 microg/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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptation, Physiological*
  • Animals
  • Cell Division / drug effects
  • Disease Models, Animal
  • Enteral Nutrition*
  • Glucagon-Like Peptide 2 / pharmacology*
  • Immunohistochemistry
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / physiology
  • Intestine, Small / cytology
  • Intestine, Small / growth & development
  • Intestine, Small / physiology
  • Intestine, Small / surgery
  • Male
  • Proglucagon / metabolism*
  • RNA, Messenger / metabolism
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucagon / metabolism*
  • Weight Gain

Substances

  • Glucagon-Like Peptide 2
  • RNA, Messenger
  • Receptors, Glucagon
  • Proglucagon