Immunological response to the prolonged administration of heterologous and homologous insulin in cattle.

Abstract
It has been generally assumed that the antigenicity of insulin is the result of differences in the structure of insulin obtained from different species. The experiments described have been designed to examine this hypothesis by testing the antigenicity of porcine and bovine insulin in 5 heifers each, with 5 additional heifers serving as adjuvant controls. An immunological response to the repeated administration of both heterologous porcine and homologous bovine insulin in adjuvant was observed in all insulin-injected animals. However, the response to the heterologous insulin in adjuvant was both more rapid and more pronounced. There was no response to the injection of adjuvant alone. The evidence for the immunological nature of the response was derived from 1/ changes in the electrophoretic distribution of insulin-I131 added to serum; 2/ delayed disappearance of insulin-I131 from serum in vivo; 3/ decreased hypoglycemic activity of insulin in vivo; 4/ increase in the acid ethanol extractable insulin-like activity of serum with a lesser increase in the insulin-like activity of unextracted serum; and 5/ in some instances, the presence of precipitating antibodies to insulin, although this was observed only in 2 of 5 animals immunized with heterologous insulin. As reported in detail elsewhere the pancreas of 5 animals immunized with insulin in adjuvant, either homologous or heterologous, exhibited striking lymphocytic infiltration and fibrosis limited to the islets of Langerhans. The glucose tolerance of the cattle remained normal. These findings raise important questions as to the identity of extracted pancreatic insulin with circulating insulin in plasma, and also suggest that the possible significance of immunopathological reactions of the endocrine pancreas to insulin warrants further consideration.