title: Hexarelin Protects Rodent Pancreatic Β-Cells Function from Cytotoxic Effects of Streptozotocin Involving Mitochondrial Signalling Pathways In Vivo and In Vitro.
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.
authors.affiliation: Institute of Basic Medicine Science, Xi'an Medical University, Xi'an, China.|Department of Forensic Science, School of Medicine, Xi'an Jiaotong University, Xi'an, China.|School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia.
authors.forename: Xinli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia.
authors.forename: Jiezhong
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia.
authors.forename: Chao
authors.initials: C
authors.lastname: Lin
authors.affiliation: Gene Cology Research Centre, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Maroochydore, QLD, Australia.
authors.forename: Renfu
authors.initials: R
authors.lastname: Shao
authors.affiliation: Department of Forensic Science, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Yan
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D003603:Cytotoxins / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects*; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013311:Streptozocin / Q000633:toxicity*; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D003603:Cytotoxins; D007328:Insulin; D009842:Oligopeptides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C086184:hexarelin; D013311:Streptozocin; D053148:Caspase 3; D053453:Caspase 9