Effect of Modification of Insulin on Its Degradation and Biological Activity. ∗

Abstract

Summary

The biological activity and rate of degradation of 9 derivatives of insulin were studied in the eviscerated-nephrectomized rabbit. Derivatives of insulin made with methanol, diazotized sulfanilic acid, formaldehyde, or hydrogen peroxide, did not affect insulin degradation; those made with 2, 4 - dinitrofluorobenzene, bis - diazobenzidine, bis-diazobenzidine-albumin, and sodium hypochlorite impaired insulin degradation. Those reagents which interfered with the rate at which insulin was degraded also destroyed the biological activity of insulin. However, the reactive groups on the insulin molecule which were essential for biological activity were not necessarily centers of attack by the destructive enzymes. It is concluded that degradation of insulin-I¹³¹ observed in physiological systems is not necessarily a function of insulin action on target tissues.