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) were treated for 14 days with IGF-I or long R (LR3IGF-I; 0, 44, 111, or 278 micrograms/day) delivered by osmotic minipumps. Both peptides induced a dose-dependent increase in gastrointestinal tissue weight. Total gut weight, small intestinal weight, and small intestinal length increased by 43, 47, and 13%, respectively, after treatment with 278 micrograms/day of LR3IGF-I. Crypt depth and villus height increased after peptide treatment with an associated increased crypt cell population (+33%), cells per villus column (+34%), and villus cell density (+20%). Proportional increments in proliferating cell nuclear antigen labeling and an unaltered crypt growth fraction indicated that the balance between the proliferative and maturation compartment of the crypt was maintained. Fecal nitrogen excretion was significantly reduced in rats treated with LR3IGF-I, suggesting an increased absorptive capacity of the duodenum. The enhanced potency of LR3IGF-I supports previous findings that the gut is especially responsive to analogues with reduced binding affinity to IGF-binding proteins.