The glomerular basement membrane of the rabbit kidney on long-term treatment with heterologous insulin preparations of different purity.

Abstract

A total of 90 rabbits were treated with monocomponent insulin (MC Actrapid Novo) and a+b component (proinsulin, intermediates, “dimer”, high-molecular proteins) and their solvents for 3 months without Freund's adjuvant. The insulin-binding capacity of the serum, as an expression of the antibody titre, as well as the light and electron microscopic structure of the glomerular basement membrane were studied. It was shown that on treatment with MC insulin there was no significant antibody formation and no increased occurrence of subepithelial, hump-like, basement membrane protuberances. In contrast, following immunization with a+b component there was a significantly higher antibody titre and a pronounced increase in nodular basement membrane changes of the glomeruli. The findings show that the impurities (a+b component) in the insulins in normal commercial usage are evidently responsible for the higher antigenicity. Further, it can be demonstrated that investigations of glomerular structures allow one to draw conclusions as to the degree of the antigenicity of different insulin preparations although the actual cause of the increased occurrence of basement membrane changes with increasing antigenicity of the insulin preparation is still unclarified. Possible causes which ought to be discussed are deposition of immune complexes and/or increased and structurally atypical basement membrane synthesis.