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-mu-l/h intraluminal IGF-I infusion produced an approximate doubling of mucosal wet weight (NaCl 50 mg vs. IGF-I 102-mu-g/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.