Diabetes Mellitus in Rabbits Immunized with Insulin

Abstract

Normal rabbits immunized with bovine insulin in adjuvant produce circulating autoantibodies that bind large amounts of endogenous insulin (measured by an immunoassay which distinguishes endogenous and exogenous insulin). In a series of nine immunized animals, two not only produced autoantibody but also, as a result of the autoimmune phenomenon, became acutely diabetic. Their blood sugar, circulating antibody, endogenous insulin bound to antibody and morphologic lesions in the islets of Langerhans observed by light and electron microscopy were compared to those of immunized but nondiabetic rabbits for a period of sixty-five weeks. Diabetes was characterized by weight loss, lipemia and blood sugar levels maintained at 350 to 600 mg. per 100 ml. throughout an experimental period of twenty-one weeks after immunization with insulin. Although circulating antibody levels were unusually high in the diabetic animals, little antibody-bound insulin was evidenced in contrast to the nondiabetic immunized rabbits whose bound endogenous insulin ranged fiom 390 to 2,340 μU. per ml. Histologic examination by light and electron microscopy at twenty-one weeks revealed absence of beta cell granules and severe damage to the beta cells. Lymphocytic infiltration of the islets was noted in the less severe diabetic in which some beta cells remained, but neither lymphocytes nor beta cells could be detected in the most severely diabetic animal. Alpha cells in each rabbit were normal. Significantly, the nondiabetic immunized rabbits also showed specific changes in their beta cells detectable by electron microscopy. The surviving, less severely diabetic rabbit remained diabetic and had detectable antibody until sacrificed fourteen months after immunization. Improvement of the animal at this time was indicated by a blood sugar level of 174 mg. per 100 ml., an increase in antibody-bound endogenous insulin, extractable pancreatic insulin in an amount two thirds of normal, and demonstrable granules in most of the beta cells. It was concluded thai an autoimmune diabetes that closely resembles the early juvenile form can be created in rabbits by immunization with insulin. The possibility that autoimmunity can not only contribute to the diabetic state in insulin-treated subjects but may prove important as an underlying cause in some forms of diabetes is discussed.

Spontaneous diabetes in dogs and cats

“…The first hypothesis is supported by the occurence of eases of diabetes after viral infectious diseases, such as mumps. The autoimmune hypothesis has received considerable support from recent experimental work [21,30,12]. Several groups of authors have succeeded in reproducing these lesions experimentally with procedures involving an immuno-pathological reaction.…”

Renovascular Hypertension in Rats Immunized with Angiotensin II

“…Endogenously formed histamine could thus be immunologically inactivated. Similarly, the effects of endogenous gastrin (12), insulin (13), and angiotensin (1) were abolished by immunization with the respective substances. Immunization with insulin not only elevated blood glucose concentrations but also effected permanent diabetes (13).…”

“…Similarly, the effects of endogenous gastrin (12), insulin (13), and angiotensin (1) were abolished by immunization with the respective substances. Immunization with insulin not only elevated blood glucose concentrations but also effected permanent diabetes (13). Accordingly, several examples illustrate a pathogenetic role of, or conversely, a prophylactic effect of antibodies against physiologically or pathophysiologically active lowmolecular substances.…”

Antigen Inhibition on Antibody Forming Cells at the Level of Effector Cell

“…Habicht et al (1975) observed the autoantibody to thyroglobulin and thyroiditis in rabbits which had been immunized with the immune complex madefrom rabbit thyroglobulin and anti-rabbit thyroglobulin serum. Grodsky et al (1966) observed the presence of the autoantibody to insulin in rabbits which had received injections of bovine insulin. Streilein et al (1975) suggested that the autoanti bodies of Fl hybrid hamsters afflicted with systemic graft-vs-host disease, which is regarded as oneof the ideal models of autoimmune diseases, might result from the allogenic effect by whichthe donor T cells attacked the host B cells and stimulated herefore quiescent self reactive clones.…”