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GLP-2 administration results in increased proliferation but paradoxically an adverse outcome in a juvenile piglet model of short bowel syndrome.

作者信息

Pereira-Fantini Prue M, Nagy Eva S, Thomas Sarah L, Taylor Russell G, Sourial Magdy, Paris Monique C J, Holst Jens J, Fuller Peter J, Bines Julie E

机构信息

Intestinal Failure and Clinical Nutrition Group, Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia.

出版信息

J Pediatr Gastroenterol Nutr. 2008 Jan;46(1):20-8. doi: 10.1097/01.mpg.0000304449.46434.06.

DOI:10.1097/01.mpg.0000304449.46434.06
PMID:18162829
Abstract

OBJECTIVE

The objective of the present study was to examine the effect of glucagon-like peptide-2 (GLP-2) administration in a piglet, juvenile model of short bowel syndrome.

MATERIALS AND METHODS

Four-week-old piglets underwent either a sham operation or 75% small bowel resection. Postoperatively, piglets received either polymeric infant formula diet or the diet and subcutaneous human recombinant GLP-2 (1600 microg/day for 7 days, 800 microg/day thereafter). Food intake was monitored throughout the experiment, and stool and serum samples obtained fortnightly. After the piglets were killed, tissues were obtained from the duodenum, jejunum, ileum, and terminal ileum, and used for morphological and functional analysis.

RESULTS

Treatment with GLP-2 resulted in significantly increased numbers of proliferating and apoptotic cells in the ileum of sham and small bowel resection piglets (P < 0.05). GLP-2 administration resulted in decreased weight gain, serum albumin, and disaccharidases in both sham and small bowel resection piglets (P < 0.001 compared with polymeric infant formula diet alone).

CONCLUSIONS

This is the first study to our knowledge to examine the effect of GLP-2 administration in a juvenile short bowel syndrome model. Contrary to adult rodent studies, administration of GLP-2 resulted in adverse outcomes including reduced ability to gain weight; decreased serum albumin, tissue maltase, and sucrase; and villous atrophy. We anticipate this information will have important implications for future paediatric clinical trials.

摘要

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