Synergistic effect of supplemental enteral nutrients and exogenous glucagon-like peptide 2 on intestinal adaptation in a rat model of short bowel syndrome
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Synergistic effect of supplemental enteral nutrients and exogenous glucagon-like peptide 2 on intestinal adaptation in a rat model of short bowel syndrome. / Liu, Xiaowen; Nelson, David W; Holst, Jens Juul; Ney, Denise M.
In: Uden navn, Vol. 84, No. 5, 11.2006, p. 1142-50.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Synergistic effect of supplemental enteral nutrients and exogenous glucagon-like peptide 2 on intestinal adaptation in a rat model of short bowel syndrome
AU - Liu, Xiaowen
AU - Nelson, David W
AU - Holst, Jens Juul
AU - Ney, Denise M
PY - 2006/11
Y1 - 2006/11
N2 - 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.
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.
KW - Adaptation, Physiological
KW - Animals
KW - Cell Division
KW - Disease Models, Animal
KW - Drug Synergism
KW - Drug Therapy, Combination
KW - Enteral Nutrition
KW - Glucagon-Like Peptide 2
KW - Intestinal Mucosa
KW - Intestine, Small
KW - Male
KW - Parenteral Nutrition, Total
KW - RNA, Messenger
KW - Random Allocation
KW - Rats
KW - Rats, Sprague-Dawley
KW - Short Bowel Syndrome
KW - Sucrase
KW - Treatment Outcome
M3 - Journal article
C2 - 17093168
VL - 84
SP - 1142
EP - 1150
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
SN - 0002-9165
IS - 5
ER -
ID: 132050503