title: Exogenous glucagon-like peptide-2 (GLP-2) augments GLP-2 receptor mRNA and maintains proglucagon mRNA levels in resected rats.
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.
authors.affiliation: Department of Nutritional Sciences, University of Wisconsin, Madison, WI, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Koopmann
authors.forename: David W
authors.initials: DW
authors.lastname: Nelson
authors.forename: Sangita G
authors.initials: SG
authors.lastname: Murali
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.forename: Mark S
authors.initials: MS
authors.lastname: Brownfield
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Denise M
authors.initials: DM
authors.lastname: Ney
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D004750:Enteral Nutrition; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D007421:Intestine, Small / Q000166:cytology / Q000254:growth & development / Q000502:physiology / Q000601:surgery; D008297:Male; D052336:Proglucagon / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000378:metabolism*; D015430:Weight Gain
chemical_list: D053767:Glucagon-Like Peptide 2; D012333:RNA, Messenger; D018027:Receptors, Glucagon; D052336:Proglucagon