Streptozotocin interactions with pancreatic beta cells and the induction of insulin-dependent diabetes.
The MSZ diabetic male mouse represents one of the most useful tools available to researchers interested in analyzing the consequences of insulin dependent diabetes in male mice. In contrast to the high mortality induced by single high doses of SZ, protracted administration of smaller SZ dosages yields a more stable diabetic condition. Moreover, in insulitis prone strains such as BKs, the model allows "synchronization" of beta cell destruction such that the inflammatory events occur on a predictable timescale. The MSZ-diabetic mouse represents a diabetic condition in which the primary etiopathologic effect is produced by an environmental toxin, and not by a genetically programmed loss of tolerance to beta cell specific antigens. In this regard, etiopathogenesis in the MSZ model is quite distinct from that underlying autoimmune type I diabetes in humans, NOD mice, and BB rats, and it is probably not appropriate to refer to pathogenesis in the MSZ model as one of "autoimmune insulitis" as has sometimes been done. The fact that insulitis in the MSZ model may not be "autoimmune," but may actually be a normal response to either tissue damage or to beta cells that have been structurally modified by a chemical, makes the model of special interest. Clearly, there is no single cause of insulin dependent diabetes, with disease induction representing a genetic susceptibility interacting with environmental triggers, such as toxins in the diet (including nitrosamines and fungal metabolites) as well as pathogenic viruses. The MSZ model will continue to be actively investigated because of insights it will afford regarding the genetic bases for susceptibility and resistance to diabetogenic environmental toxins. The model will be of further value by contributing to knowledge of the complicated interactions between pancreatic islet cells, other endocrine cells, and leukocytes in maintenance of glucose homeostasis.
Wilson
G L
GL
Department of Structural and Cellular Biology University of South Alabama, Mobile 36688.
Leiter
E H
EH
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D006801:Humans; D007107:Immune System / Q000187:drug effects; D007515:Islets of Langerhans / Q000187:drug effects*; D051379:Mice; D013311:Streptozocin / Q000494:pharmacology*
D013311:Streptozocin