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Dynamin-related protein 1 mediates high glucose induced pancreatic beta cell apoptosis

Men, Xiuli
Li, Mi
Cai, Hanqing
Xu, Shiqin
Zhang, Wenjian
Xu, Yaping
Ye, Liya
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Published in International Journal of Biochemistry & Cell Biology. 2009, vol. 41, no. 4, p. 879-90
Abstract The pancreatic beta cell dysfunction is critical cycle in the pathogenesis of diabetes. Hyperglycemia is one of factors that induce pancreatic beta cell dysfunction, but the underlying mechanisms have not been well elucidated. In this study, we reported that a mitochondrial fission modulator, Dynamin-related protein 1 (Drp-1), plays an important role in high glucose induced beta cell apoptosis. Drp-1 expressed in islet beta cells was increased drastically under hyperglycemia conditions. Induction of Drp-1 expression significantly promoted high glucose induced apoptosis in Drp-1WT (Drp-1 wild type) inducible beta cell line, but not in Drp-1K38A (a dominant negative mutant of Drp1) inducible beta cell line. We further demonstrated that mitochondrial fission, cytochrome C release, mitochondrial membrane potential decreased, caspase-3 activation and generation of reactive oxygen species were enhanced by induction of Drp-1WT, but prevented by Drp-1K38A in pancreatic beta cells under high glucose condition. These results indicated that Drp-1 mediates high glucose induced pancreatic beta cell apoptosis.
Keywords AnimalsApoptosis/physiologyCaspase 3/metabolismCell LineCytochromes c/metabolismDiabetes Mellitus, Type 2/metabolism/pathologyDisease Models, AnimalFlow CytometryGTP Phosphohydrolases/genetics/metabolismGlucose/metabolismHumansImmunohistochemistryIn Situ Nick-End LabelingInsulin-Secreting Cells/cytology/metabolism/physiologyMaleMicroscopy, Electron, TransmissionMicrotubule-Associated Proteins/genetics/metabolismMitochondrial Proteins/genetics/metabolismRatsRats, WistarReactive Oxygen Species/metabolismReverse Transcriptase Polymerase Chain Reaction
PMID: 18805504
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MEN, Xiuli et al. Dynamin-related protein 1 mediates high glucose induced pancreatic beta cell apoptosis. In: International Journal of Biochemistry & Cell Biology, 2009, vol. 41, n° 4, p. 879-90. doi: 10.1016/j.biocel.2008.08.031 https://archive-ouverte.unige.ch/unige:33543

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Deposited on : 2014-01-22

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