Synergistic effect of supplemental enteral nutrients and exogenous glucagon-like peptide 2 on intestinal adaptation in a rat model of short bowel syndrome

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.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).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)).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.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.