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Evidence-Based Complementary and Alternative Medicine
Volume 2011 (2011), Article ID 231938, 10 pages
http://dx.doi.org/10.1155/2011/231938
Research Article

Protective Mechanism of KIOM-4 in Streptozotocin-Induced Pancreatic β-Cells Damage Is Involved in the Inhibition of Endoplasmic Reticulum Stress

1School of Medicine, Jeju National University, Jeju-si 690-756, Republic of Korea
2Diabetic Complication Research Center, Division of Traditional Korean Medicine Integrated Research, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea

Received 19 June 2010; Accepted 27 August 2010

Copyright © 2011 Rui Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Endoplasmic reticulum stress-mediated apoptosis plays an important role in the destruction of pancreatic β-cells and contributes to the development of type 1 diabetes. The present study examined the effect of KIOM-4, a mixture of four plant extracts, on streptozotocin- (STZ-) induced endoplasmic reticulum (ER) stress in rat pancreatic β-cells (RINm5F). KIOM-4 was found to inhibit STZ-induced apoptotic cell death, confirmed by formation of apoptotic bodies and DNA fragmentation. STZ was found to induce the characteristics of ER stress; mitochondrial Ca2+ overloading, enhanced ER staining, release of glucose-regulated protein 78 (GRP78), phosphorylation of RNA-dependent protein kinase (PKR) like ER kinase (PERK) and eukaryotic initiation factor-2α (eIF-2α), cleavage of activating transcription factor 6 (ATF6) and caspase 12, and upregulation of CCAAT/enhancer-binding protein-homologous protein (CHOP). However, KIOM-4 attenuated these changes induced by STZ. Furthermore, KIOM-4 suppressed apoptosis induced by STZ in CHOP downregulated cells using CHOP siRNA. These results suggest that KIOM-4 exhibits protective effects in STZ-induced pancreatic β-cell damage, by interrupting the ER stress-mediated pathway.