**Acknowledgement**

244 Apoptosis and Medicine

DR5 and/or DR4 death receptors, thus enhancing TRAIL-induced apoptosis (Haupt S., et al. 2003; Kelley R.F., et al. 2005). Our studies provide evidence for activation of TRAIL-induced apoptosis in pancreatic β-cells by administration of streptozotocin on models of

Mitochondrial-mediated apoptotic pathway plays an important role in the development of pancreatic islet damage in diabetes mellitus (Sakurai K., et al. 2001). In alloxan-induced diabetes intracellular calcium homeostasis is typically impaired. *In vitro* and *in vivo* experiments have shown that cytoplasmic calcium concentrations increase in the cells of pancreatic islets. This effect is due to depolarization of cell and mitochondrial membranes of βendocrine cells which is associated with excessive entry of calcium from the extracellular fluid and intracellular calcium mobilization (Crow M.T., et al. 2004; Jung J.Y., et al. 2004). Thus, considerable gross damage to the intracellular structures by free radicals, oxidation of SHproteins and impairment of intracellular calcium homeostasis typically result in necrosis and

apoptosis, with necrotic processes being more common in alloxan-induced diabetes.

Comparison of morphological data and the dynamics of impairment of β-cell functional activity in experimental models (alloxan-, streptozotocin-, nicotinamide-streptozotocininduced and immune-dependent diabetes) gives insight into the pathogenesis of experimental diabetes. A high apoptotic index and the prevalence of destructive processes, which enable us to assess not only the extent of pancreatic tissue damage but also to evaluate biochemical parameters, such as plasma glucose, insulin, C-peptide, etc., can be used as markers of severity of experimental diabetes (Snigur G.L., Smirnov A.V. 2010).

Thus, apoptosis is a complex, multi-step, poorly regulated process. Any regulatory impairment can lead to the development of pathological changes in the endocrine apparatus of pancreatic islets including the development of experimental diabetes (Reed J.C., Green D.R. 2011). Each level and element of this system is a potential drug target. The significance of apoptosis determines the need for the refocusing of biomedical research from theoretical biology to clinical medicine. Investigation of apoptotic mechanisms in various pathological conditions enable us to make more accurate diagnoses and prognoses as well as to adjust therapy. The possibility of deliberate control of apoptotic processes is considered to be the basis for developing new medications used to treat many socially important diseases,

Experimental diabetic rats exhibited significant pathohistological changes in the pancreatic islets caused by cytotoxine (streptozotocin+CFA) at all levels of tissue structure. The development of diabetes mellitus was associated with decreased volume fraction of pancreatic islets and β-cells due to inflammation (insulitis) and pronounced destructive

*Department of Pathologic Anatomy, Volgograd State Medical University, Russia* 

streptozotocin-induced and immune-dependent diabetes.

including the development of anti-diabetic drugs.

changes (e.g. necrosis and apoptosis).

A.V. Smirnov and G.L. Snigur

**Author details** 

We express our gratitude to the Head of pharmacology department of Volgograd State Medical University, Academician of Russian Academy for Medical Sciences, Honored Scientist of Russia, MD, full professor, Spasov Alexander A., assistant professor of pharmacology department of Volgograd State Medical University, PhD, Cheplyaeva Natalia I., assistant professor of pharmacology department of Volgograd State Medical University, PhD, Chepurnova Mariya V. for their assistance in conducting the present study.
