**Acknowledgement**

This work has been supported by Special subsidy for promotion of higher level education & research in private universities from Japanese Ministry of Education,Culture,Sports,Science & Technology and Showa University Joint Research grant. The authors thank the graduate students and fellows who contributed to the studies.

<sup>\*</sup> Corresponding Author

#### **9. References**

218 Apoptosis and Medicine

mediated and ER stress-mediated apoptosis. Taken together, we propose a diagram

Apoptosis is involved in various diseases, and affects a wide variety of organs including the liver, kidney, central nervous system, and heart. This field of research has been increasingly active in both basic medical sciences and clinical levels, and in the future, when novel findings are obtained on how changes in the process of apoptosis lead to aggravation or improvement of diseases, an innovative strategy for more effective therapy will be designed.

This work has been supported by Special subsidy for promotion of higher level education & research in private universities from Japanese Ministry of Education,Culture,Sports,Science & Technology and Showa University Joint Research grant. The authors thank the graduate

showing the mechanism of hepatocyte apoptosis as seen in Fig. 8.

**Figure 8.** Schematic diagram of apoptotic pathway.

and Katsuji Oguchi

students and fellows who contributed to the studies.

Progress of elucidation of apoptotic process is greatly sought after.

*Department of Pharmacology, Showa University, School of Medicine, Tokyo, Japan* 

**8. Conclusion** 

**Author details** 

**Acknowledgement** 

Corresponding Author

Mayumi Tsuji\*

 \*


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**Chapter 9** 

© 2012 Smirnov et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**Pancreatic Islet Beta-Cell Apoptosis** 

For screening and detailed studying of antidiabetic medications, various genetic and nongenetic experimental models of diabetes mellitus were used (Islam S., Loots D.T. 2009). And though they are not absolutely equivalent to etiopathogenetic mechanisms of human pathological conditions, each of them represents itself as an integral tool for research into genetic, endocrine, metabolic, morphological changes of this disease (Sarvilina I.V.,

The most commonly used diabetic experimental models are non-genetic models that use hydrophilic β-cell glucose analogues, such as alloxan, streptozotocin, chlorozotocin, cyproheptadine, etc. The common mechanism of action of these substance includes degradation of pancreatic islet β-cells by means of: 1) generation of oxygen free radicals that destroy the integrity of a cell, 2) alkylation of DNA and subsequent activation of poly-ADPribose-synthetase - reduction of NAD to β-cell, and 3) inhibition of active transport of calcium and calmodulin-activated protein kinase (Rees D.A., Alcolado J.C. 2005). In this type of experimental models of diabetes mellitus streptozotocin (an N-nitrosourea derivative of glucosamine) is most commonly used (McNeill J.H. 1999). Depending on cytotoxin dosage used in the experiment (45-70 mg/kg) and route of administration (i.p., i.v.), it is possible to model and simulate different states of carbohydrate metabolism based on a specific clinical type of diabetes mellitus (DM mixed (type 1-2) latent or «hidden» diabetes) (Srinivasan K. et al. 2007). Although diabetes mellitus usually has obvious clinical symptoms such as hyperglycemia, glucosuria, polyuria, polydipsia, severe weight loss, it is difficult to measure the contribution of each of the links to the pathogenesis of diabetes and to assess the extent of pancreatic islet β-cell damage and death. The toxic effect of alloxan and streptozotocin on cells in pancreatic islets manifests itself not only by necrosis but also by apoptosis of pancreatic islet β-cells (Daisy Mythili M., et al. 2004). The study of apoptotic mechanisms

**in Experimental Diabetes Mellitus** 

A.V. Smirnov, G.L. Snigur and M.P. Voronkova

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/51411

**1. Introduction** 

Maclakov Y.S. 2008).


**Chapter 9** 
