Immunochemical Distinction between Insulins with Identical Amino-Acid Sequences

Abstract

VIRTUALLY all human subjects treated with commercial mixtures of beef-pork insulin develop circulating insulin-binding antibodies that are readily detectable with insulin labelled with iodine-131 by means of paper or starch eleetrophoresis, paper chromatography or ultracentrifugation¹. These antibodies react not only with the specific immunizing insulins but also with horse, sheep and human insulins², and with dog, monkey, rabbit and whale insulins (unpublished work) in greater or lesser degree. Harris, Sanger and Naughton³ have shown that the amino-acid sequences of insulins from four different ungulate species (cattle, pig, horse and sheep) differ only in the 8–10 positions of the A chains. Although some human antisera react quite similarly with these four insulins, certain antisera can distinguish clearly among insulins from the different species, generally reacting much more strongly with beef and sheep insulins than with pork and horse insulins². These differences in reaction of the ungulate insulins have been related² to the known differences in the 8–10 sequence of the A-chain or to possible differences in secondary or tertiary structure.