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

TY - JOUR

T1 - GLP-2 administration results in increased proliferation but paradoxically an adverse outcome in a juvenile piglet model of short bowel syndrome

AU - Pereira-Fantini, Prue M

AU - Nagy, Eva S

AU - Thomas, Sarah L

AU - Taylor, Russell G

AU - Sourial, Magdy

AU - Paris, Monique C J

AU - Holst, Jens Juul

AU - Fuller, Peter J

AU - Bines, Julie E

PY - 2008/1

Y1 - 2008/1

N2 - 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.

AB - 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.

KW - Animals

KW - Apoptosis

KW - Cell Division

KW - Disease Models, Animal

KW - Female

KW - Glucagon-Like Peptide 2

KW - Humans

KW - Intestine, Small

KW - Recombinant Proteins

KW - Serum Albumin

KW - Short Bowel Syndrome

KW - Sucrase

KW - Swine

KW - Weight Gain

KW - alpha-Glucosidases

U2 - 10.1097/01.mpg.0000304449.46434.06

DO - 10.1097/01.mpg.0000304449.46434.06

M3 - Journal article

C2 - 18162829

SN - 0277-2116

VL - 46

SP - 20

EP - 28

JO - Journal of Pediatric Gastroenterology and Nutrition

JF - Journal of Pediatric Gastroenterology and Nutrition

IS - 1

ER -