Drak2 overexpression results in increased beta-cell apoptosis after free fatty acid stimulation.
Drak2 is a serine threonine kinase in the death-associated protein family. In this study, we investigated its role in free fatty acid (FFA)-induced islet apoptosis. Drak2 mRNA and protein were rapidly induced in islet beta-cells after FFA stimulation. Such Drak2 upregulation was accompanied by increased beta-cell apoptosis, which was inhibited by Drak2 knockdown using siRNA. Conversely, transgenic (Tg) Drak2 overexpression led to aggravated beta-cell apoptosis triggered by FFA. Drak2 overexpression in islets compromised the increase of anti-apoptotic factors, such as Bcl-2, Bcl-xL and Flip, upon FFA assault. Further in vivo experiments demonstrated that Drak2 Tg mice presented compromised glucose tolerance in a diet-induced obesity model. Our data show that Drak2 is detrimental to islet survival in the presence of excessive lipid.
Mao
Jianning
J
Laboratory of Immunology, Centre Hospitalier de l'Université de Montréal (CHUM), Notre Dame Hospital, Montreal, Quebec, Canada.
Luo
Hongyu
H
Wu
Jiangping
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D004032:Diet; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D050417:Insulin-Secreting Cells / Q000166:cytology*; D051379:Mice; D009765:Obesity; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000494:pharmacology; D012333:RNA, Messenger; D015854:Up-Regulation / Q000187:drug effects
D051017:Apoptosis Regulatory Proteins; D005230:Fatty Acids, Nonesterified; D012333:RNA, Messenger; C495197:Drak2 protein, mouse; D017346:Protein Serine-Threonine Kinases