Beta cell destruction in the development of autoimmune diabetes in the non-obese diabetic (NOD) mouse.
In the non-obese diabetic (NOD) mouse model of Type 1 (insulin-dependent) diabetes, evidence suggests that pancreatic beta cells are destroyed in part by apoptotic mechanisms. The precise mechanisms of beta cell destruction leading to diabetes remain unclear. The NOD mouse has been studied to gain insight into the cellular and molecular mediators of beta cell death, which are discussed in this review. Perforin, secreted by CD8(+) T cells, remains one of the only molecules confirmed to be implicated in beta cell death in the NOD mouse. There are many other molecules, including Fas ligand and cytokines such as interferon-gamma, interleukin-1 and tumor necrosis factor-alpha, which may lead to beta cell destruction either directly or indirectly via regulation of toxic molecules such as nitric oxide. As beta cell death can occur in the absence of perforin, these other factors, in addition to other as yet unidentified factors, may be important in the development of diabetes. Effective protection of NOD mice from beta cell destruction may therefore require inhibition of multiple effector mechanisms.
Thomas
H E
HE
The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria 3050, Australia.
Kay
T W
TW
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology*; D053222:Fas Ligand Protein; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D019014:fas Receptor / Q000276:immunology
D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor