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.