A study to elucidate the role of VAMP7 in insulin secretion from pancreatic beta-cells.

• Project/Area Number: 15K19525
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Kyorin University
• Principal Investigator: Aoyagi Kyota 杏林大学, 医学部, 講師 (50453527)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: インスリン分泌 / 糖尿病 / オートファジー

Outline of Final Research Achievements

VAMP family proteins are SNARE proteins, which mediate fusions between intracellular vesicles and their target membranes. VAMP2, VAMP3, VAMP4, VAMP7, VAMP8 are expressed in pancreatic beta-cells, but the physiological role of VAMP7 in insulin secretion from pancreatic beta-cells were remained to be elucidated. In this study, I found that VAMP7 regulates autophagy to maintain mitochondrial homeostasis and to control insulin secretion in pancreatic beta-cells. I also found that maintenance of mitochondrial homeostasis would play a critical role in pathology of type 2 diabetes mellitus.

Research Products

• [Journal Article] Opposing roles for SNAP23 in secretion in exocrine and endocrine pancreatic cells (2016)
  • Author(s): Masataka Kunii, et al,
  • Journal Title: J. Cell Biol. Volume: 215 Issue: 1 Pages: 121-138
  • DOI: 10.1083/jcb.201604030
  • Peer Reviewed / Open Access
• [Journal Article] VAMP7 regulates autophagy to maintain mitochondrial homeostasis and to control insulin secretion in pancreatic beta-cells. (2016)
  • Author(s): Aoyagi K, Ohara-Imaizumi M, Itakura M, Torii S, Akimoto Y, Nishiwaki C, Nakamichi Y, Kishimoto T, Kawakami H, Harada A, Takahashi M, Nagamatsu S
  • Journal Title: Diabetes Volume: 65 Issue: 6 Pages: 1648-1659
  • DOI: 10.2337/db15-1207
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A gain-of-function mutation in NALCN in a child with intellectual disability, ataxia, and arthrogryposis. (2015)
  • Author(s): Aoyagi K, Rossignol E, Hamdan FF, Mulcahy B, Xie L, Nagamatsu S, Rouleau GA, Zhen M, Michaud JL
  • Journal Title: Human Mutation Volume: 36 Issue: 8 Pages: 753-757
  • DOI: 10.1002/humu.22797
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 膵β細胞におけるVAMP7を介したオートファジー制御機構とその生理作用 (2016)
  • Author(s): 青柳共太
  • Organizer: 第10回オートファジー研究会
  • Place of Presentation: 新潟
  • Year and Date: 2016-11-14
• [Presentation] VAMP7 regulates autophagy to maintain mitochondrial homeostasis and to control insulin secretion in pancreatic beta-cells. (2016)
  • Author(s): 青柳共太、西脇知世乃、中道洋子、岸本拓磨、鳥居征司、今泉美佳
  • Organizer: 第８９回日本生化学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-25
• [Presentation] VAMP7はオートファジーを制御してミトコンドリアの恒常性維持と第２相インスリン分泌を調節する (2015)
  • Author(s): 青柳共太、今泉美佳、板倉誠、鳥居征司、秋元義弘、西脇知世乃、中道洋子、岸本拓磨、原田彰宏、高橋正身、永松信哉
  • Organizer: 第38回日本分子生物学会年会、第88回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] VAMP7はオートファジーによるミトコンドリア恒常性維持機構を介して膵β細胞からの第２相インスリン分泌を制御する (2015)
  • Author(s): 青柳共太、今泉美佳、板倉誠、鳥居征司、岸本拓磨、西脇知世乃、中道洋子、秋元義弘、原田彰宏、高橋正身、永松信哉
  • Organizer: 第67回日本細胞生物学会大会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-30