Glucagonlike peptide-2 analogue enhances intestinal mucosal mass after ischemia and reperfusion

Background/Purpose: Glucagonlike peptide-2 (GLP-2), a product of the posttranslational processing of proglucagon, has been shown to enhance mucosal mass and function in both normal intestine and in the residual intestine after massive small bowel resection. This study was designed to determine if a synthetic, protease-resistant analogue of GLP-2 (GLP-2 alpha) can enhance mucosal mass in small intestine after ischemia and reperfusion (I/R) injury. Methods: Ten young adult male Sprague-Dawley rats underwent laparotomy and superior mesenteric artery occlusion for a period of 40 minutes. During this period of ischemia, each rat underwent placement of a jugular Venous catheter that was connected to a subcutaneously placed osmotic pump designed to deliver its contents over 3 days. The rats were divided into 2 groups based on the contents of the pumps: group 1, saline at 1 mu L/h (n = 6) and group 2, GLP-2 alpha at 100 mu g/kg/d (n = 4). Three days after insertion of the pumps the small intestine was harvested from the surviving rats for determination of mucosal DNA and protein content. Statistical analysis was performed using unpaired Student's t test. Results: After I/R injury to the small intestine, a 3-day systemic infusion of GLP-2 alpha significantly increased mucosal DNA content 41% (P <.05) and mucosal protein content 60% (P <.05) when compared with saline-treated controls. In addition, infusion of GLP-2 alpha reduced mortality from 50% to 25%. Conclusions: These data show for the first time that GLP-2 alpha enhances mucosal mass following I/R injury to the small intestine. GLP-2 alpha may be of benefit to patients with intestinal ischemia syndromes such as necrotizing enterocolitis and midgut volvulus. J Pediatr Surg 35:357-359. Copyright (C) 2000 by W.B. Saunders Company.