**3.3 Apoptosis as the final mechanism of immune-mediated destruction of pancreatic b-cells**

The most important stage in the pathogenesis of T1DM is the dysregulation of apoptosis processes associated with the preservation of autoreactive clones of lymphocytes that are tropic for b-cells and are able to "escape" from apoptosis [11].

To date, most studies in the field of studying the role of apoptosis of immunemediated destruction of pancreatic b-cells in T1DM have been performed on experimental models of type 1 diabetes mellitus in vivo and in vitro. However, it should be emphasized that the induction and regulation of apoptosis in animal models of T1DM may differ significantly in T1DM in humans [2]. In particular, nicotinamide, which effectively protects rat b-cells from apoptosis [43], can protect human b-cells from necrosis caused by free radicals, but not from cytokine-induced apoptosis [44]. Data obtained in experiments in vitro show that the sensitivity of human b-cells is definitely lower than that of animal b-cells [45, 46], which must be considered when approximating the results from model systems to the human body.

The detection of apoptosis in vivo and the study of its role in the destruction of b-cells in T1DM encounters significant methodological difficulties. However, in some models of T1DM in experimental animals, it is possible to detect apoptosis in pancreatic b-cells and show a correlation between the degree of insulitis and apoptosis of b-cells. In particular, it has been shown that apoptosis is the predominant mechanism of b-cell death in NOD mice [11].
