Rates of Production of Alanine and Heptapeptide and of Loss of Biological Activity during Digestion of Insulin with Trypsin

Abstract

SUMMARY A sample of desoctapeptide-insulin, obtained by the action of trypsin on insulin, was essentially inactive, having less than 2 y0 of intact insulin, in lowering the blood sugar of rabbits. A sample of synthetic heptapeptide, Gly-Phe-Phe-Tyr-Thr- Pro-Lys (5), which was identical with that released by the action of trypsin on bovine insulin, possessed less than 0.1 y0 of the activity of intact insulin in the mouse convulsion test. The rates of release of alanine and heptapeptide and of the loss of biological activity during the digestion of insulin with trypsin were found to follow essentially the same kinetics. From the above data, it is concluded that, in contrast with the report of Nicol (3), desoctapeptide-insulin possesses very low or no antidiabetogenic properties and that some portion of the octapeptide, removed by the action of trypsin on insulin, is re- quired for the biological activity insulin. Acknowledgments-The authors would like to thank Miss Sharon L. Hayes and Mr. A. Hirotoshi Nishikawa for aid in the