Luminal Stability of Insulin-Like Growth Factors I and II in Developing Rat Gastrointestinal Tract

BACKGROUND:Insulin-like growth factors (IGF)-I and -II are present in milk of a number of mammalian species. The stability of IGF-I and -II in the intestinal lumen was investigated by measuring the proteolytic degradation of I-labeled IGF-I and IGF-II by rat (suckling and adult) intestinal luminal flushings in vitro. METHODS:Degradation of I-labeled IGF-I and IGF-II was assessed by measuring the generation of acid-soluble radioactivity and the reduction of the amounts of peak activity (gel filtration). Degradation was confirmed by measuring the loss of immunoreactivity and receptor activity. RESULTS:Incubation of I-IGF-I with midjejunal luminal flushings from 12-day-old suckling rats generated acid-soluble radioactivity in a time- and dose-(flushing) dependent manner, whereas incubation of I-IGF-II produced only minor amounts of acid-soluble radioactivity. Degradation activity in luminal flushings from adult rat intestine was several times greater than that in luminal flushings from suckling rats. Degradation of I-IGF-II was several times lower than that of I-IGF-I in the intestinal luminal flushings from suckling and adult rats. The rate of decrease in immunoprecipitable I-IGF-I was considerably lower than the rate of decrease in receptor-active radioactivity. Except for immunoreactivity, analyses of acid-precipitable, peak-A, and receptor-active radioactivities demonstrate that IGF-II is relatively more stable than IGF-I in luminal flushings of suckling rat duodenum, jejunum, and midjejunum. CONCLUSIONS:These results show that the stability of IGF in the gastrointestinal lumen depends on the age of the animal and the segment of the gastrointestinal tract, as well as on the peptide isoform.