Summary
Mice immunized with once crystallized or chromatographed insulin at various doses throughout a period of three months, in order to investigate “tolerance induction” to different insulin preparations, unexpectedly revealed lymphocytic infiltrates in the endocrine and exocrine pancreas. Peri-insulitis, periductulitis and sometimes interstitial pancreatitis were observed both in animals injected with chromatographed insulin or once crystallized insulin, which can be fractionated into true Sanger insulin, a number of insulin compounds including proinsulin, and many undefined proteins of higher molecular weight. While the occurrence of periductulitis was not dependent on dosage, peri-insulitis was only found with certain dose ranges in both groups. Injections of once crystallized insulin evoked peri-insular infiltrates at a low dosage, injections of chromatographed insulin at a high dosage. The possibility is discussed as to whether or not the peri-insular and peri-ductular infiltrates reflect a cellular immune response induced by fractions of crystalline insulin, which may differ from true Sanger insulin.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Craighead, J.E., Steinke, J.: Diabetes mellitus-like syndrome in mice infected with encephalomyocarditis virus. Amer. J. Path.63, 119 (1971).
Freytag, G., Klöppel, G.: Experimentelle Insulitis und Pankreatitis nach Immunseren gegen Pankreasextrakte verschiedener Reinheitsgrade. Beitr. path. Anat.39, 138 (1969).
Gepts, W.: Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes14, 619 (1965).
Jansen, F.K.: Tolerance to high and low doses of natural crystalline insulin. Diabetologia7, 290–292 (1971a).
Jansen, F.K.: The ability of MC-insulin or1 X crystallized insulin in the development of immunological tolerance in mice. Diabetologia7, 485 (1971b) Abstr.
Klöppel, G., Altenähr, E., Freytag, G.: Studies on ultra-structure and immunology of the insulitis in rabbits immunized with insulin. Virchows Arch. Abt. A. Path. Anat.356, 1–15 (1972).
Lacy, P.E., Wright, P.H.: Allergic intestitial pancreatitis in rats injected with guinea pig anti-insulin serum. Diabetes14, 634 (1965).
LeCompte, P.M.: “Insulitis” in early juvenile diabetes. Arch. Path.66, 450 (1958).
LeCompte, P.M., Steinke, J., Soeldner, J.S., Renold, A.E.: Changes in the islets of Langerhans in cows injected with heterologous and homologous insulin. Diabetes15, 586 (1966).
LeCompte, P.M., Legg, M.A.: Insulitis (lymphocytic infiltration of pancreatic islets) in late-onset diabetes. Diabetes21, 762–769 (1972).
Lee, J.C., Grodsky, G.M., Caplan, C.J., Craw, L.: Experimental immune diabetes in the rabbit. Amer. J. Path.57, 597 (1969).
Logothetopoulos, J., Bell, E.G.: Histological and autoradiographic studies of the islets of mice injected with insulin antibody. Diabetes15, 205 (1966).
von Meyenburg, H.: Über “Insulitis” bei Diabetes. Schweiz. med. Wsehr.70, 247 (1940).
Müntefering, H., Schmidt, W.A.K., Körber, W.: Zur Virusgenese des Diabetes mellitus bei der weißen Maus. Dtsch. med. Wschr.96, 693 (1971).
Renold, A.E., Soeldner, J.S., Steinke, J.: Immunological studies with homologous and heterologous pancreatic insulin in the cow. Ciba Foundation Colloquia Endocrinol.15, 122 (1964).
Renold, A.E., Gonet, A.E., Vecchio, D.: Immunopathology of the endocrine pancreas. In: Textbook of Immunopathology, ed. by P.A. Miescher and H.J. Müllereberhard. Vol. II, p. 595. New York and London: Grune and Stratton 1969.
Schlichtkrull, J., Brange, J., Fge, H., Hallund, O., Heding, L.G., Christiansen, A.H., Jorgensen, K., Markussen, J., Stahnke, P., Sundby, F., Volund, A.: Proinsulin and related proteins. European Association for the Study of Diabetes. 5th annual meeting, Montpellier 1969.
Steiner, H.: Insulitis beim perakuten Diabetes des Kindes. Klin. Wschr.46, 417 (1968).
Steiner, D.F., Hallund, O., Rubenstein, A., Cho, S., Bayliss, C.: Isolation and proterties of proinsulin, intermediate froms and other minor components from crystalline bovine insulin. Diabetes17, 725 (1968).
Toreson, W.E., Feldman, R., Lee, J.C., Grodsky, G.M.: Pathology of diabetes mellitus produced in rabbits by means of immunization with beef insulin. Amer. J. clin. Path.42, 531 (1964).
Weber, E.: Grundriß der biologischen Statistik, 6. Aufl. Jena: Gustav Fischer Verlag 1967.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Freytag, G., Jansen, P.K. & Klöppel, G. Immune reactions to fractions of crystalline insulin. Diabetologia 9, 185–190 (1973). https://doi.org/10.1007/BF01219781
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01219781