GLP-2 administration results in increased proliferation but paradoxically an adverse outcome in a juvenile piglet model of short bowel syndrome
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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. / Pereira-Fantini, Prue M; Nagy, Eva S; Thomas, Sarah L; Taylor, Russell G; Sourial, Magdy; Paris, Monique C J; Holst, Jens Juul; Fuller, Peter J; Bines, Julie E.
In: Journal of Pediatric Gastroenterology and Nutrition, Vol. 46, No. 1, 01.2008, p. 20-8.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 46
SP - 20
EP - 28
JO - Journal of Pediatric Gastroenterology and Nutrition
JF - Journal of Pediatric Gastroenterology and Nutrition
SN - 0277-2116
IS - 1
ER -
ID: 132049538