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

Int J Biochem Cell Biol. 2009 Apr;41(4):879-90. doi: 10.1016/j.biocel.2008.08.031. Epub 2008 Sep 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Caspase 3 / metabolism
  • Cell Line
  • Cytochromes c / metabolism
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Disease Models, Animal
  • Dynamins
  • Flow Cytometry
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • Glucose / metabolism*
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / physiology*
  • Male
  • Microscopy, Electron, Transmission
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction


  • Microtubule-Associated Proteins
  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • Cytochromes c
  • Caspase 3
  • GTP Phosphohydrolases
  • DNM1L protein, human
  • Dynamins
  • Glucose