Abstract
Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, intestinotrophic hormone derived from post-translational processing of proglucagon in the distal bowel. Parenterally-fed rats showed a synergistic intestinal growth response to combination treatment with enteral nutrients (EN) and a low-dose of intravenous GLP-2 (Am J Physiol 295:R1794, 2008). Evidence suggest that whey protein may inhibit dipeptidyl peptidase-IV (DPP-IV) and prolong the half life of GLP-2. The objective of this study was to determine what enteral protein component is responsible for the synergistic intestinal growth induced by treatment with EN + GLP-2. Rats were randomized to 7 treatment groups (n=6) maintained with parenteral nutrition (PN) and continuous intravenous infusion of GLP-2 (100 μg/kg bw/day) for 7 days. The control group received only PN+GLP-2. Six treatment groups received PN+GLP2 from days 1-3 and partial PN+GLP-2 plus EN from a semi-elemental liquid diet from days 4-7 (n=6). Enteral protein was provided from different sources as follows: Casein, Soy, and 4 groups receiving different combinations of whey protein, whey protein concentrate (WPC), hydrolyzed WPC, WPC + hydrolyzed WPC, and soy + WPC + hydrolyzed WPC. The 4 groups receiving whey protein showed significantly increased mucosa growth in ileum for dry mass, protein, and DNA by approximately 20%, 22% and 30%-49% compared to Casein, Soy or the PN+GLP-2 control, respectively. All groups that received EN showed significantly greater jejunal sucrase segmental activity and gain of body weight after 7 days of PN compared to the PN+GLP-2 control. This suggests that during PN, any form of a supplemental complete enteral diet improves digestive capacity and gain in body weight irrespective of protein source. There was a significant 35% greater concentration of plasma bioactive GLP-2 in 5 out of the 6 groups that received EN, compared to the PN+GLP-2 control. All groups that received EN showed greater proglucagon mRNA expression in ileum compared to the PN+GLP-2 control. Increased proglucagon mRNA and plasma bioactive GLP-2 are consistent with nutrient regulation of GLP-2. The 3 groups receiving hydrolyzed WPC showed significantly lower plasma DPP-IV activity compared to Casein or Soy. In addition, the 4 groups receiving EN that included whey protein showed significantly decreased DPP-IV specific activity in ileum and colon compared to Casein or Soy. In conclusion, the synergistic ileal mucosa growth due to combination treatment with EN+GLP2 in rats with PN-induced mucosal atrophy is associated with intake of whey protein which may mediate this effect through decreasing DPP-IV activity.
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