Trophic action of local intraileal infusion of insulin-like growth factor I: polyamine dependence.
Experiments were performed to determine potential growth-promoting effects of human recombinant insulin-like growth factor I (hrIGF-I) in the gastrointestinal tract. IGF-I and IGF-II, but not insulin, were potent (half-maximal effective concentration 0.3 nM) and efficacious inducers of the growth-related enzyme ornithine decarboxylase (ODC) in the gut-derived cell line IEC-6. Maximal ODC induction was observed after treatment of cells with 10 nM IGF-I. In whole animal experiments, bolus intraileal injection of 10 nM hrIGF-I in anesthetized rats induced a 300% increase in ileal mucosal ODC activity, which was sensitive to inhibition with difluoromethylornithine (DFMO). Rats were implanted intraperitoneally with osmotic minipumps filled with 0.9% NaCl or 10 nM IGF-I that was delivered to the ileal lumen by a short Silastic catheter. Sixty-six hours of 1 microliter/h intraluminal IGF-I infusion produced an approximate doubling of mucosal wet weight (NaCl 50 mg vs. IGF-I 102 micrograms/2 cm mucosa) and total mucosal RNA, DNA, and protein content over that in rats that were infused with NaCl. Intraperitoneal treatment with 200 mg/kg DFMO three times per day had little effect on ileal mucosal mass, but completely inhibited the trophic response to IGF-I infusion. IGF-I infusion had no effect on body weight.
Olanrewaju
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H
Department of Physiology, School of Medicine, East Carolina University, Greenville, North Carolina 27858.
Patel
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L
Seidel
E R
ER
D000818:Animals; D006801:Humans; D007082:Ileum / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D007267:Injections; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins
D011073:Polyamines; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D009955:Ornithine Decarboxylase