GLP-2α accelerates recovery of mucosal absorptive function after intestinal ischemia/reperfusion

Background/Purpose: The authors' previous laboratory results have shown that rats treated for 3 days with intravenous GLP-2 alpha, a synthetic protease-resistant form of glucagonlike peptide-2, showed increased mucosal mass and absorptive function when compared with saline-treated controls after intestinal ischemia/reperfusion (I/R). This study was designed to explore the temporal relationship between injury that occurs secondary to intestinal I/R and recovery of mucosal absorptive function with and without GLP-2 alpha treatment. Methods: Each of 18 male Sprague-Dawley rats (300 to 333 g)was subjected to superior mesenteric artery occlusion for 30 minutes, during which time a jugular venous catheter was placed and connected to a subcutaneous infusion pump. Rats were divided into 4 groups based on the type and duration of infusion as follows: group 1, systemic saline at 1 muL/h for 24 hours (n = 5); group 2, systemic GLP-2 alpha at 100 mug/kg/d for 24 hours (n = 5); group 3, systemic saline at 1 muL/h for 72 hours (n = 4); and group 4, systemic GLP-2a at 100 mug/kg/d for 72 hours (n = 4). Immediately after the infusions, C-14-galactose and C-14-glycine absorption was measured using an in vivo, closed-recirculation technique and expressed as micromoles per square centimeter intestine +/- SEM. Statistical analysis was performed using analysis of variance. Results: Twenty-four hours after intestinal I/R injury, there was a decrease in substrate absorption but no significant difference between the saline and GLP-2 alpha -treated groups (galactose absorption, 1.13 +/- 0.09 in group 1 v 1.35 +/- 0.11 in group 2, P = .15; glycine absorption, 1.18 +/- 0.13 in group 1 v 1.34 +/- 0.15 in group 2, P = .36). However, after the 72-hour infusion, absorption of galactose and glycine was significantly increased in the rats receiving GLP-2a as compared with the saline-infused control group (galactose absorption, 1.24 +/- 0.13 in group 3 v 1.88 +/- 0.10 in group 4, P < .01; glycine absorption, 1.64 <plus/minus> 0.07 in group 3 v 2.05 +/- 0.08 in group 4, P < .05). Compared with previously determined levels of absorption in normal, uninjured rat intestine (1.50 <plus/minus> 0.12 mu mol/cm(2) for galactose and 1.85 +/- 0.17 mu mol/cm(2) for glycine), after I/R a 72-hour infusion of GLP-2 alpha increased galactose absorption 26% (P < .05) and glycine absorption 11% (P = .29) beyond baseline. Conclusions: When initiated at the time of intestinal I/R, a continuous infusion of GLP-2<alpha> accelerated recovery of mucosal absorptive function in rats. Remarkably, carbohydrate absorption at 72 hours was increased to a level significantly greater than that in normal, uninjured rat intestine.