Inhibition of insulin degradation by insulin-like growth factors.

The effect of insulin-like growth factors (IGF 1 and IGF 2) on insulin degradation was studied with the use of a preparation of insulin protease from rat skeletal muscle. Insulin, IGF 1 and IGF 2 inhibited 125I insulin degradation by this enzyme. IGF 2 was the most potent inhibitor and IGF 1 was the least potent. These results are similar to what has been reported previously for the insulin-degrading activity in the serum of a diabetic patient who was resistant to sc and im insulin. Insulin protease also degraded 125I-iodoIGF 1 and 125I-iodoIGF 2. 125I-iodoIGF 2 was degraded more rapidly than was l25I iocioIGF 1. 125I-iodoinsul in was degraded more rapidly than 125I-iOCioIGF 2. With all three peptides, immunoprecipitation was a more sensitive measure of degradation than was trichloroacetic acid precipitation. The results suggest that insulin protease may be responsible for the degradation of insulin-like growth factors as well as of insulin.