TRUNCATED AND NATIVE INSULIN-LIKE GROWTH FACTOR-I ENHANCE MUCOSAL ADAPTATION AFTER JEJUNOILEAL RESECTION

被引:134
作者
VANDERHOOF, JA
MCCUSKER, RH
CLARK, R
MOHAMMADPOUR, H
BLACKWOOD, DJ
HARTY, RF
PARK, JHY
机构
[1] CREIGHTON UNIV,SCH MED,DEPT PEDIAT,OMAHA,NE 68178
[2] UNIV NEBRASKA,MED CTR,OMAHA,NE 68105
[3] UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27514
[4] GENENTECH INC,DEPT DEV BIOL,SAN FRANCISCO,CA 94080
关键词
D O I
10.1016/0016-5085(92)90318-S
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 > 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. © 1992.
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页码:1949 / 1956
页数:8
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