Truncated and native insulinlike growth factor I enhance mucosal adaptation after jejunoileal resection

Abstract

It has been shown previously that insulinlike growth factors (IGFs) stimulate the proliferation of intestinal crypt cells in vitro. To examine the in vivo effects of IGF-I on mucosal adaptation, three groups of Sprague-Dawley rats underwent 80% jejunoileal resection. Miniosmotic pumps were then inserted under the skin immediately after resection to deliver vehicle (resected control), 1.5 mg/kg per day of IGF-I, or 1.5 mg/kg per day of des-(1-3)-IGF-I (des-IGF-I). Des-IGF-I is a truncated form of IGF-I that binds as well to type I IGF receptors but less tightly to several forms of IGF-binding proteins (IGFBPs) than IGF-I. Ad libitum food intake did not differ among the three resected groups. Body weight gains were greater in animals receiving des-IGF-I than in those receiving IGF-I, which were greater than resected controls. All animals were killed 7 days postoperatively, and the remaining small intestine was removed and divided at the anastomotic site. Both IGF-I and des-IGF-I induced hyperplasia (increased DNA and protein content) in the duodenojejunum but not in the ileum. IGF-I and des-IGF-I were equally active. In contrast, sucrase, maltase, and leucine aminopeptidase activities were greater only in the ileum of animals receiving IGF-I and des-IGF-I than in resected controls. Although more potent in stimulating overall body weight gain, des-IGF-I was not more potent than IGF-I when duodenal and ileal responses were determined. IGF infusion (IGF-I greater than des-IGF-I) increased the levels of circulating IGFBP-3 and IGFBP-2, which may act to modulate the biological effectiveness of the infused peptides. These results suggest that both IGF-I and des-IGF-I may have potential as therapeutic agents for short bowel patients.