Hexarelin protects rodent pancreatic B-cells function from cytotoxic effects of streptozotocin involving mitochondrial signalling pathways in vivo and in vitro

Zhao, Yan, Zhang, Xinli, Chen, Jiezhong, Lin, Chao, Shao, Renfu, Yan, Chunxia and Chen, Chen (2016) Hexarelin protects rodent pancreatic B-cells function from cytotoxic effects of streptozotocin involving mitochondrial signalling pathways in vivo and in vitro. PLoS ONE, 11 2: . doi:10.1371/journal.pone.0149730


Author Zhao, Yan
Zhang, Xinli
Chen, Jiezhong
Lin, Chao
Shao, Renfu
Yan, Chunxia
Chen, Chen
Title Hexarelin protects rodent pancreatic B-cells function from cytotoxic effects of streptozotocin involving mitochondrial signalling pathways in vivo and in vitro
Formatted title
Hexarelin protects rodent pancreatic B-cells function from cytotoxic effects of streptozotocin involving mitochondrial signalling pathways in vivo and in vitro
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2016-02-26
Sub-type Article (original research)
DOI 10.1371/journal.pone.0149730
Open Access Status DOI
Volume 11
Issue 2
Total pages 15
Place of publication San Francisco, United States
Publisher Public Library of Science
Language eng
Formatted 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 pro-apoptotic 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Biomedical Sciences Publications
 
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