Whey protein potentiates the intestinotrophic action of glucagon-like peptide-2 in parenterally fed rats

Am J Physiol Regul Integr Comp Physiol. 2009 Nov;297(5):R1554-62. doi: 10.1152/ajpregu.00423.2009. Epub 2009 Sep 23.


Glucagon-like peptide-2 (GLP-2) is a nutrient-regulated intestinotrophic hormone derived from proglucagon in the distal intestine. Enteral nutrients (EN) potentiate the action of GLP-2 to reverse parenteral nutrition (PN)-induced mucosal hypoplasia. The objective was to determine what enteral protein component, casein, soy, or whey protein, potentiates the intestinal growth response to GLP-2 in rats with PN-induced mucosal hypoplasia. Rats received PN and continuous intravenous infusion of GLP-2 (100 microg/kg/day) for 7 days. Six EN groups received PN+GLP-2 for days 1-3 and partial PN+GLP-2 plus EN for days 4-7. EN was provided by ad libitum intake of a semielemental liquid diet with different protein sources: casein, hydrolyzed soy, whey protein concentrate (WPC), and hydrolyzed WPC+casein. Controls received PN+GLP-2 alone. EN induced significantly greater jejunal sucrase activity and gain of body weight, and improved feed efficiency compared with PN+GLP-2 alone. EN induced greater ileal proglucagon expression, increased plasma concentration of bioactive GLP-2 by 35%, and reduced plasma dipeptidyl peptidase IV (DPP-IV) activity compared with PN+GLP-2 alone, P < 0.05. However, only whey protein, and not casein or soy, potentiated the ability of GLP-2 to reverse PN-induced mucosal hypoplasia and further increase ileal villus height, crypt depth, and mucosa cellularity compared with PN+GLP-2 alone, P < 0.05. The ability of whey protein to induce greater mucosal surface area was associated with decreased DPP-IV activity in ileum and colon compared with casein, soy, or PN+GLP-2 alone, P < 0.05. In conclusion, whey protein potentiates the action of GLP-2 to reverse PN-induced mucosal hypoplasia in association with decreased intestinal DPP-IV activity.

Publication types

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

MeSH terms

  • Animals
  • Body Weight / physiology
  • Dipeptidyl Peptidase 4 / metabolism
  • Dose-Response Relationship, Drug
  • Eating / physiology
  • Glucagon-Like Peptide 2 / blood
  • Glucagon-Like Peptide 2 / pharmacology*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / growth & development
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects*
  • Intestines / growth & development*
  • Male
  • Milk Proteins / pharmacology*
  • Models, Animal
  • Parenteral Nutrition*
  • Proglucagon / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sucrase / metabolism
  • Whey Proteins


  • Glucagon-Like Peptide 2
  • Milk Proteins
  • Whey Proteins
  • Proglucagon
  • Sucrase
  • Dipeptidyl Peptidase 4