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Am J Physiol Regul Integr Comp Physiol 297: R1554-R1562, 2009. First published September 23, 2009; doi:10.1152/ajpregu.00423.2009
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Articles

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

Xiaowen Liu,1 Sangita G. Murali,1 Jens J. Holst,2 and Denise M. Ney1

1Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin; and 2Department of Medical Physiology, the Panum Institute, University of Copenhagen, Copenhagen, Denmark

Submitted July 16, 2009 ; accepted in final form September 18, 2009

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 µg/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.

mucosal growth; proglucagon; dipeptidyl peptidase-IV; whey protein concentrate



Address for reprint requests and other correspondence: D. M. Ney, Univ. of Wisconsin-Madison, Dept. of Nutritional Sciences, 1415 Linden Drive, Madison, WI 53706 (e-mail: ney{at}nutrisci.wisc.edu).







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