PMID- 17093168 OWN - NLM STAT- MEDLINE DCOM- 20061214 LR - 20230318 IS - 0002-9165 (Print) IS - 0002-9165 (Linking) VI - 84 IP - 5 DP - 2006 Nov TI - Synergistic effect of supplemental enteral nutrients and exogenous glucagon-like peptide 2 on intestinal adaptation in a rat model of short bowel syndrome. PG - 1142-50 AB - BACKGROUND: Short bowel syndrome (SBS) can lead to intestinal failure and require total or supplemental parenteral nutrition (TPN or PN, respectively). Glucagon-like peptide 2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that stimulates intestinal adaptation. OBJECTIVE: Our objective was to determine whether supplemental enteral nutrients (SEN) modulate the intestinotrophic response to a low dose of GLP-2 coinfused with PN in a rat model of SBS (60% jejunoileal resection plus cecectomy). DESIGN: Rats were randomly assigned to 8 treatments by using a 2 x 2 x 2 factorial design and maintained with either TPN or PN for 7 d. The 3 main treatment effects were the following: transection or resection (TPN alone), +/- SEN (days 4-6), and +/- GLP-2 (100 mug . kg body wt(-1) . d(-1)). RESULTS: The treatments induced differential growth of duodenal and jejunal mucosa. Significant differences in villus height, crypt depth, dry mass, and concentrations of protein and DNA were observed between the treatments and TPN alone (SEN: 15-59% increase; GLP-2: 14-84% increase; and SEN + GLP-2: 63-160% increase). Plasma concentrations of bioactive GLP-2 were significantly greater with GLP-2 infusion (TPN alone: 25 +/- 9 pmol/L; SEN: 29 +/- 10 pmol/L; GLP-2: 59 +/- 31 pmol/L; SEN + GLP-2: 246 +/- 40 pmol/L) and correlated with mucosal growth. Jejunal sucrase activity (in U/cm) was significantly greater with SEN than without SEN. SEN + GLP-2 induced dramatic mucosal growth and greater plasma concentration of GLP-2 (SEN x GLP-2 interaction, P < 0.0001). Resection significantly increased expression of proglucagon mRNA in colon. CONCLUSIONS: Combination treatment with SEN and GLP-2 induced a synergistic response resulting in greater mucosal cellularity and digestive capacity in parenterally fed rats with SBS. This shows that SEN improve the intestinotrophic response to exogenous GLP-2, possibly by stimulating enterocyte proliferation and differentiation. FAU - Liu, Xiaowen AU - Liu X AD - Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA. FAU - Nelson, David W AU - Nelson DW FAU - Holst, Jens J AU - Holst JJ FAU - Ney, Denise M AU - Ney DM LA - eng GR - R01-42835/PHS HHS/United States GR - T32-07665/PHS HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Clin Nutr JT - The American journal of clinical nutrition JID - 0376027 RN - 0 (Glucagon-Like Peptide 2) RN - 0 (RNA, Messenger) RN - EC 3.2.1.48 (Sucrase) SB - IM MH - *Adaptation, Physiological MH - Animals MH - Cell Division/drug effects MH - Disease Models, Animal MH - Drug Synergism MH - Drug Therapy, Combination MH - *Enteral Nutrition MH - Glucagon-Like Peptide 2/*pharmacology MH - Intestinal Mucosa/*drug effects/growth & development MH - Intestine, Small/drug effects/pathology/surgery MH - Male MH - *Parenteral Nutrition, Total MH - RNA, Messenger/metabolism MH - Random Allocation MH - Rats MH - Rats, Sprague-Dawley MH - Short Bowel Syndrome/*therapy MH - Sucrase/metabolism MH - Treatment Outcome EDAT- 2006/11/10 09:00 MHDA- 2006/12/15 09:00 CRDT- 2006/11/10 09:00 PHST- 2006/11/10 09:00 [pubmed] PHST- 2006/12/15 09:00 [medline] PHST- 2006/11/10 09:00 [entrez] AID - S0002-9165(23)29161-3 [pii] AID - 10.1093/ajcn/84.5.1142 [doi] PST - ppublish SO - Am J Clin Nutr. 2006 Nov;84(5):1142-50. doi: 10.1093/ajcn/84.5.1142.