title: 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.
authors.affiliation: Department of Pediatrics, Creighton University School of Medicine, Omaha, Nebraska.
authors.forename: J A
authors.initials: JA
authors.lastname: Vanderhoof
authors.forename: R H
authors.initials: RH
authors.lastname: McCusker
authors.forename: R
authors.initials: R
authors.lastname: Clark
authors.forename: H
authors.initials: H
authors.lastname: Mohammadpour
authors.forename: D J
authors.initials: DJ
authors.lastname: Blackwood
authors.forename: R F
authors.initials: RF
authors.lastname: Harty
authors.forename: J H
authors.initials: JH
authors.lastname: Park
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects*; D000818:Animals; D002352:Carrier Proteins / Q000097:blood; D004247:DNA / Q000032:analysis; D007082:Ileum / Q000601:surgery*; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000737:chemistry / Q000502:physiology*; D007583:Jejunum / Q000601:surgery*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011506:Proteins / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D010446:Peptide Fragments; D011506:Proteins; C058957:insulin-like growth factor 1, des-(1-3)-; D007334:Insulin-Like Growth Factor I; D004247:DNA