Investigation of the role of Semaphorin 3G in the homeostasis of pancreatic alpha cells and the application to the therapy against diabetes.

• Project/Area Number: 26461326
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Chiba University
• Principal Investigator: Kawamura Harukiyo 千葉大学, 大学院医学研究院, 特任准教授 (70527902)
• Co-Investigator(Kenkyū-buntansha): 小林 一貴 千葉大学, 大学院医学研究院, 特任准教授 (30400998) ; 竹本 稔 千葉大学, 大学院医学研究院, 特任教授 (60447307) ; 徳山 宏丈 千葉大学, 大学院医学研究院, 特任助教 (90385039)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: セマフォリン3G / グルカゴン / 膵α細胞

Outline of Final Research Achievements

This study was performed on the basis of the hypothesis that Semaphorin 3G (Sema3G) regulated glucagon secretion and contribute to the homeostasis of glucose metabolism.
Analysis of Sema3G deficient mice shows increase of pancreatic α cells and elevated expression of pancreas duodenum homeobox 1 (Pdx1) and Neurogenen3 (Ngn3), transcription factors essential for the differentiation and function maintenance of pancreatic endocrine cells. On the other hand, serum glucagon level was low and it was found that nerve cells were increased on the periphery of pancreatic islets and sympathetic nerve ending intruded into islets. These results indicates that Sema3G plays an important role in glucagon secretion by regulating proliferation and differentiation of pancreatic α cells and the organization of nerve network.

Research Products

• [Journal Article] Pituitary adenylate cyclase-activating polypeptide protects glomerular podocytes from inflammatory injuries. (2015)
  • Author(s): Sakamoto K, Kuno K, Takemoto M, He P, Ishikawa T, Onishi S, Ishibashi R, Okabe E, Shoji M, Hattori A, Yamaga M, Kobayashi K, Kawamura H, Tokuyama H, Maezawa Y, Yokote K
  • Journal Title: J Diabetes Res Volume: 印刷中 Pages: 727152-727152
  • DOI: 10.1155/2015/727152
  • Peer Reviewed / Open Access
• [Journal Article] Enhanced vascular endothelial growth factor signaling in islets contributes to β cell injury and consequential diabetes in spontaneously diabetic Torii rats. (2014)
  • Author(s): Mukai E, Ohta T, Kawamura H, Lee EY, Morita A, Sasase T, Miyajima K, Inagaki N, Iwanaga T, Miki T
  • Journal Title: Diabetes Res Clin Pract Volume: 106(2) Pages: 303-311
  • Peer Reviewed
• [Journal Article] Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin compared with alpha-glucosidase inhibitor in Japanese patients with T2DM inadequately controlled on sulfonylurea alone (SUCCESS-2): a multicenter, randomized, open-label, non-inferiority trial. (2014)
  • Author(s): Kobayashi K, Yokoh H, Sato Y, Takemoto M, Uchida D, Kanatsuka A, Kuribayashi N, Terano T, Hashimoto N, Sakurai K, Hanaoka H, Ishikawa K, Onishi S,Yokote K, on behalf of the SUCCESS Study Group.
  • Journal Title: Diabetes, Obesity and Metabolism Volume: - Issue: 8 Pages: 761-765
  • DOI: 10.1111/dom.12264
  • Peer Reviewed
• [Presentation] Functional analysis of Semaphorin 3G in atherosclerosis development. (2015)
  • Author(s): Masaya Yamaga, Harukiyo Kawamura, Kazuki Kobayashi, Hirotake Tokuyama, Yoshiro Maezawa, Takahiro Ishikawa, Ryouichi Ishibashi, Kenichi Sakamoto, Akiko Hattori, Mayumi Shoji, Peng He, Minoru Takemoto, Koutaro Yokote.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場(大阪府大阪市)
  • Year and Date: 2015-04-24
• [Presentation] Semaphorin 3Gの粥状動脈硬化形成における機能解析 (2015)
  • Author(s): 山賀 政弥、河村 治清、小林 一貴、徳山 宏丈、前澤 善朗、石川 崇広、石橋 亮一、坂本 憲一、井出佳奈、竹本 稔、横手 幸太郎.
  • Organizer: 第52回日本臨床分子医学会学術集会
  • Place of Presentation: みやこめっせ(京都府京都市)
  • Year and Date: 2015-04-10
• [Presentation] 粥状動脈硬化形成におけるSemaphorin 3Gの機能解析 (2014)
  • Author(s): 山賀 政弥、河村 治清、竹本 稔、小林 一貴、徳山 宏丈、前澤 善朗、石川 崇広、大西 俊一郎、石橋 亮一、賀 鵬、北本 匠、坂本 憲一、服部 暁子、正司 真弓、横手 幸太郎
  • Organizer: 第29回 日本糖尿病合併症学会
  • Place of Presentation: 都市センターホテル(東京都千代田区)
  • Year and Date: 2014-10-03 – 2014-10-04
• [Presentation] Combinatorial therapy of cilostazol and probucol effectively reduces albuminuria through inhibition of proinflammatory pathways in podocytes. (2014)
  • Author(s): Peng He, Harukiyo Kawamura, Minoru Takemoto, Kyoko Kuno, Mayumi Shoji, Akiko Hattori, Masaya Yamaga, Kenichi Sakamoto, Emiko Okabe, Ryoichi Ishibashi, Takahiro Ishikawa, Shunichiro Onishi, Yoshiro Maezawa, Hirotake Tokuyama, Kazuki Kobayashi, Koutaro Yokote
  • Organizer: 50th EASD annual meeting
  • Place of Presentation: Reed Exhibitions Messe Wien congress center(ｳｨｰﾝ, ｵｰｽﾄﾘｱ)
  • Year and Date: 2014-09-15 – 2014-09-19
• [Presentation] Protective effect of Semaphorin 3G on atherosclerosis development. (2014)
  • Author(s): Masaya Yamaga, Harukiyo Kawamura, Kazuki Kobayashi, Hirotake Tokuyama, Takahiro Ishikawa,Ryouichi Ishibashi, Kenichi Sakamoto, Akiko Hattori, Peng He, Minoru Takemoto, Koutaro Yokote
  • Organizer: 9th Metabolic Syndrome, Type2 Diabetes and Atherosclerosis Congress
  • Place of Presentation: 京都国際会議場(京都府京都市)
  • Year and Date: 2014-09-12 – 2014-09-14
• [Presentation] 粥状動脈硬化形成におけるSemaphorin 3Gの機能解析 (2014)
  • Author(s): 山賀 政弥、河村 治清、竹本 稔、小林 一貴、徳山 宏丈、前澤 善朗、石川 崇広、石橋 亮一、賀 鵬、坂本 憲一、服部 暁子、正司 真弓、横手 幸太郎
  • Organizer: 第46回 日本動脈硬化学会総会 学術集会
  • Place of Presentation: 京王プラザホテル(東京都新宿区)
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] 腎糸球体ポドサイトにおけるシロスタゾール/プロブコールの相加的抗炎症メカニズム (2014)
  • Author(s): 賀 鵬、河村 治清、藤本 昌紀、小林 一貴、石川 崇広、大西 俊一郎、石橋 亮一、岡部 恵見子、竹本 稔、横手 幸太郎
  • Organizer: 第57回 日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪国際会議場(大阪府大阪市)
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] 粥状動脈硬化形成におけるSemaphorin 3Gの機能解析 (2014)
  • Author(s): 山賀 政弥、河村 治清、竹本 稔、小林 一貴、徳山 宏丈、前澤 善朗、石川 崇広、大西 俊一郎、石橋 亮一、賀 鵬、北本 匠、坂本 憲一、服部 暁子、正司 真弓、横手 幸太郎
  • Organizer: 第57回 日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪国際会議場(大阪府大阪市)
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] Protective effect of cilostazol/probucol on inflammatory kidney injury (2014)
  • Author(s): He P, Kawamura H, Kobayashi K, Tokuyama H, Ishikawa T, Onishi S, Ishibashi R, Okabe E, Kitamoto T, Sakamoto K, Yamaga M, Hattori A, Shoji M, Kuno K, Yan Kunimasa, Takemoto M and Yokote K
  • Organizer: The 18th International Vascular Biology Meeting
  • Place of Presentation: みやこメッセ(京都府京都市)
  • Year and Date: 2014-04-14 – 2014-04-17
• [Presentation] Protective effect of Semaphorin 3G on atherosclerosis development (2014)
  • Author(s): Yamaga M, Kawamura H, Kobayashi K, Tokuyama H, Ishikawa T, Onishi S, Ishibashi R, Okabe E, Sakamoto K, Hattori A, Shoji M, He P, Takemoto M and Yokote K
  • Organizer: The 18th International Vascular Biology Meeting
  • Place of Presentation: みやこメッセ(京都府京都市)
  • Year and Date: 2014-04-14 – 2014-04-17