Purpose: Glucagonlike peptide-2 (GLP-2) is a 33-amino acid peptide that appears to be highly tissue specific for the intestine. This study was designed to examine the effect of systemically administered GLP-2 on intestinal absorptive function and mucosal mass, and determine the in vivo dose-response curves for this new peptide.
Methods: Twenty-five young adult male Sprague-Dawley rats had placement of jugular venous catheters connected to subcutaneously placed osmotic minipumps. The rats were divided into five groups based on the contents in the osmotic pump: group 1 (control, n = 5) normal saline and groups 2, 3, 4, and 5 (n = 5 each) were given GLP-2 at 5, 50, 250, and 500 microg/kg/d, respectively. After a 14-day infusion, [C14] galactose and [C14] glycine absorption were measured in a 10-cm segment of midsmall intestine using an in vivo closed-recirculation technique. Mucosal DNA content and protein content of the same small bowel segment were also determined for each group. Statistical analysis was performed by analysis of variance (ANOVA).
Results: GLP-2 significantly increased galactose absorption at a dose of 50 (P<.01), 250 (P<.01), and 500 (P<.05) microg/kg/d and glycine absorption at a dose of 50, 250, and 500 microg/kg/d (P<.01). GLP-2 also significantly increased mucosal DNA content at a dose of 50 (P<.01) and 250 (P<.05) microg/kg/d and protein content at a dose of 50 and 250 microg/kg/d (P<.01).
Conclusions: These data demonstrate that GLP-2 can enhance normal rat small intestine mucosal mass and absorption in vivo with the maximum effect seen at 50 microg/kg/d.