Dynamin-related protein 1 mediates high glucose induced pancreatic beta cell apoptosis.
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.
Men
Xiuli
X
Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, PR China.
Wang
Haiyan
H
Li
Mi
M
Cai
Hanqing
H
Xu
Shiqin
S
Zhang
Wenjian
W
Xu
Yaping
Y
Ye
Liya
L
Yang
Wenying
W
Wollheim
Claes B
CB
Lou
Jinning
J
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D034281:Dynamins; D005434:Flow Cytometry; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D053148:Caspase 3; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins; D005947:Glucose