The role of the transcription factor ETV5 in insulin exocytosis

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• 作者：Ruth Gutierrez-Aguilar (1)
  Dong-Hoon Kim (2)
  Marina Casimir (3) (4)
  Xiao-Qing Dai (3) (4)
  Paul T. Pfluger (5)
  Jongsun Park (6)
  April Haller (1)
  Elizabeth Donelan (1)
  Jisoo Park (6)
  David D’Alessio (1)
  Stephen C. Woods (7)
  Patrick E. MacDonald (3) (4)
  Randy J. Seeley (1)
  
• 关键词：Beta cell ; ETV5 ; Genome ; wide association study ; Glucose homeostasis ; Insulin exocytosis ; Insulin secretion ; Insulin sensitivity ; Transcription factor
• 刊名：Diabetologia
• 出版年：2014
• 出版时间：February 2014
• 年：2014
• 卷：57
• 期：2
• 页码：383-391
• 全文大小：449 KB
• 作者单位：Ruth Gutierrez-Aguilar (1)
  Dong-Hoon Kim (2)
  Marina Casimir (3) (4)
  Xiao-Qing Dai (3) (4)
  Paul T. Pfluger (5)
  Jongsun Park (6)
  April Haller (1)
  Elizabeth Donelan (1)
  Jisoo Park (6)
  David D’Alessio (1)
  Stephen C. Woods (7)
  Patrick E. MacDonald (3) (4)
  Randy J. Seeley (1)
  
  1. Department of Internal Medicine, University of Cincinnati, 2170 East Galbraith Road, Cincinnati, OH, 45237, USA
  2. Department of Pharmacology, Korea University College of Medicine, Seoul, South Korea
  3. Department of Pharmacology, University of Alberta, Edmonton, AB, Canada
  4. Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
  5. Institute for Diabetes and Obesity, Helmholtz Centre Munich, Neuherberg, Germany
  6. Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, South Korea
  7. Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA
  
• ISSN：1432-0428

文摘

Aims/hypothesis Genome-wide association studies have revealed an association of the transcription factor ETS variant gene 5 (ETV5) with human obesity. However, its role in glucose homeostasis and energy balance is unknown. Methods Etv5 knockout (KO) mice were monitored weekly for body weight (BW) and food intake. Body composition was measured at 8 and 16?weeks of age. Glucose metabolism was studied, and glucose-stimulated insulin secretion was measured in vivo and in vitro. Results Etv5 KO mice are smaller and leaner, and have a reduced BW and lower fat mass than their wild-type controls on a chow diet. When exposed to a high-fat diet, KO mice are resistant to diet-induced BW gain. Despite a greater insulin sensitivity, KO mice have profoundly impaired glucose tolerance associated with impaired insulin secretion. Morphometric analysis revealed smaller islets and a reduced beta cell size in the pancreatic islets of Etv5 KO mice. Knockdown of ETV5 in an insulin-secreting cell line or beta cells from human donors revealed intact mitochondrial and Ca2+ channel activity, but reduced insulin exocytosis. Conclusion/interpretation This work reveals a critical role for ETV5 in specifically regulating insulin secretion both in vitro and in vivo.