Low dose streptozotocin induced diabetes in mice. Metabolic, light microscopical, histochemical, immunofluorescence microscopical, electron microscopical and morphometrical findings

The experimental animal model of human insulin-dependent diabetes mellitus (IDDM, type I diabetes), which was for the first time described by Like and Rossini (1976) for Charles River CD-1 mice and produced by the application of multiple subdiabetogenic streptozotocin (SZ) doses, has been reproduced in the mouse strain C57 Bl/KsJ which has been bred over several generations at the Central Institute for Diabetes Karlsburg (since 1975). Male mice were given subdiabetogenic intraperitoneal injections of SZ (40 mg/kg b.w.) on five days running.--The simultaneously performed metabolic, light and electron microscopical, histochemical, fluorescence microscopical, and morphometric examinations show that the small doses of SZ lead to a metabolic disturbance in the islets of Langerhans already on the third day of the experiment (after the first two SZ injections) which is associated with a high-degree reduction or an interruption of the insulin production. Subsequently, on the 8th day (three days after the last SZ injection) up to the 20th day an insulitis occurs which is characterized by a target cell reaction of lymphocytes against the beta cells and leads to the lysis of the majority of the beta cells. In the course and after the insulitis, a persisting insulin deficiency diabetes develops with lacking signs of an attempt to replace the perished beta cells. For the time being, the nature of this target beta cell destruction by lymphocytes remains unclear. According to the enzyme-histochemical and electron microscopical results, the involved lymphocytes are natural killer cells (NK cells) rather than T cells. The release of the target cell reaction is obviously effected by the initial metabolic disturbances in the beta cells intervening in the insulin synthesis. Virus bodies do not play any role in this process. The importance of this animal model to human insulin-dependent diabetes mellitus is discussed.