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Protease Treatment Delays Diabetes Onset in Diabetes-prone Nonobese Diabetic (NOD) Mice

Wiest-Ladenburger U.,1 Richter W.,1 Moeller P.,2 Boehm B. O.1. Protease Treatment Delays Diabetes Onset in Diabetes-prone Nonobese Diabetic (NOD) Mice. Inter. Journal of Immunotherapy 1997, Vol. XIII, No. 3/4, pp. 75-78 - ISSN 0255-9625.
Inter. Journal of  Tissue Reactions 1997, Vol. XIX, No. 1/2,  abstract 108, pp. 89 - ISSN 0250-0868. SO 112 (4-12-2) (19-04-2)
1 Abteilung Innere Medizin I, Universität Ulm, Ulm, Germany; 2 Institut für Pathologie, Universität Ulm, Ulm, Germany.
7th Interscience World Conference on Inflammation, Antirheumatics, Analgesics, Immunomodulators, May 19-21, Geneva, Switzerland


It has recently been demonstrated that proteolytic enzyme treatment modulates certain immune-mediated diseases. We have, therefore, studied the effect of administration of a protease mixture in the NOD mouse, an elegant animal model for autoimmune insulin-dependent diabetes mellitus (IDDM). Female NOD mice were fed proteolytic enzymes from age 6 weeks to 10 weeks, within the subclinical phase of IDDM. Once a week animals received intragastrically 1 mg Phlogenzym® (n=10 mice) or 0.5 mg Phlogenzym®  (n=10) in 0.5 ml saline or saline only (n=10). Mice were followed for development of IDDM up to week 23. At week 21, all control animals were diabetic, whereas 25% of the treated mice were still normoglycemic at the end of the observation period. No significant appearance of autoantibodies against either isoform of the important islet cell antigen glutamic acid decarboxylase (GAD), GAD65 and GAD67, was observed in the mouse sera as determined by a highly sensitive radioimmunoassay. The histopathological examination of pancreatic islets showed signs of insulitis in all mice with a tendency of milder insulitis in the protease-treated groups.