Journal article
Hexarelin Protects Rodent Pancreatic Β-Cells Function from Cytotoxic Effects of Streptozotocin Involving Mitochondrial Signalling Pathways In Vivo and In Vitro
PLoS One, Vol.11(2), e0149730
2016
Abstract
Mitochondrial functions are crucial for pancreatic β-cell survival and glucose-induced insulin secretion. Hexarelin (Hex) is a synthetic small peptide ghrelin analogue, which has been shown to protect cardiomyocytes from the ischemia-reperfusion process. In this study, we used in vitro and in vivo models of streptozotocin (STZ)-induced β-cell damage to study the protective effect of Hex and the associated mechanisms. We found that STZ produced a cytotoxic effect in a dose- and time-dependent manner in MIN6 cells (a mouse β-cell line). Hex (1.0 μM) decreased the STZ-induced damage in β-cells. Rhodamine 123 assay and superoxide DHE production assay revealed that Hex ameliorated STZ-induced mitochondrial damage and excessive superoxide activity in β-cells. In addition, Hex significantly reduced STZ-induced expression of cleaved Caspases-3, Caspases-9 and the ratio of proapoptotic protein Bax to anti-apoptotic protein Bcl-2 in MIN6 cells. We further examined the in vivo effect of Hex in a rat model of type 1 diabetes induced by STZ injection. Hex ameliorated STZ-induced decrease in plasma insulin and protected the structure of islets from STZ-induced disruption. Hex also ameliorated STZ-induced expression of cleaved Caspase-9 and the Bax in β-cells. In conclusion, our data indicate that Hex is able to protects β- cell mass from STZ-caused cytotoxic effects involving mitochondrial pathways in vitro and in vivo. Hex may serve as a potential protective agent for the management of diabetes.
Details
- Title
- Hexarelin Protects Rodent Pancreatic Β-Cells Function from Cytotoxic Effects of Streptozotocin Involving Mitochondrial Signalling Pathways In Vivo and In Vitro
- Authors
- Yan Zhao (Author) - University of QueenslandXinli Zhang (Author) - University of QueenslandJiezhong Chen (Author) - University of QueenslandChao Lin (Author) - University of QueenslandRenfu Shao (Author) - University of the Sunshine Coast - Faculty of Science, Health, Education and EngineeringChunxia Yan (Author) - Xi'an Jiatong University, ChinaChen Chen (Author) - University of Queensland
- Publication details
- PLoS One, Vol.11(2), e0149730; 16
- Publisher
- Public Library of Science
- Date published
- 2016
- DOI
- 10.1371/journal.pone.0149730
- ISSN
- 1932-6203
- Copyright note
- Copyright © 2016 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Organisation Unit
- School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99449597202621
- Output Type
- Journal article
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- Endocrinology & Metabolism
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