PROLONGED ADMINISTRATION OF IGF PEPTIDES ENHANCES GROWTH OF GASTROINTESTINAL TISSUES IN NORMAL RATS

To investigate the effect of insulin-like growth factor (IGF) peptide infusion on the gastrointestinal tract, female rats (115 g, 6/group) w ere treated for 14 days with IGF-I or long R (LR(3)IGF-I; 0, 44, 111, or 278 mu g/day) delivered by osmotic minipumps. Both peptides induced a dose-dependent increase in gastrointestinal tissue weight. Total gu t weight, small intestinal weight, and small intestinal length increas ed by 43, 47, and 13%, respectively, after treatment with 278 mu g/day of LR(3)IGF-I. Crypt depth and villus height increased after peptide treatment with an associated increased crypt cell population (+33%), c ells per villus column (+34%), and villus cell density (+20%). Proport ional increments in proliferating cell nuclear antigen labeling and an unaltered crypt growth fraction indicated that the balance between th e proliferative and maturation compartment of the crypt was maintained . Fecal nitrogen excretion was significantly reduced in rats treated w ith LR(3)IGF-I, suggesting an increased absorptive capacity of the duo denum. The enhanced potency of LR(3)IGF-I supports previous findings t hat the gut is especially responsive to analogues with reduced binding affinity to IGF-binding proteins.