The role of Src on pancreatic β-cells and its relationship to GPCRsignal

• Project/Area Number: 23791028
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Chiba University (2012); Kyoto University (2011)
• Principal Investigator: MUKAI Eri 千葉大学, 大学院・医学研究院, 講師 (60362539)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: エネルギー / 糖質代謝異常 / 糖尿病 / 糖代謝 / インスリン分泌

Research Abstract

We have previously showed that Src activation induces ROS production and impaired insulin secretion in diabetic β-cells and GPCR ligand could suppress the Src activation and ROS production. The present study revealed that Src is involved in glucose-induced insulin secretion and its augmentation by GPCR ligand in normal state and the effect of Src is through glucokinase regulation, indicating that Src is important for insulin secretary mechanism of β-cells.

Research Products

• [Journal Article] Reduction of reactive oxygen species ameliorates metabolism-secretion coupling in islets of diabetic GK rats by suppressing lactate overproduction (2013)
  • Author(s): Sasaki M, Fujimoto S, Sato Y, Nishi Y, Mukai E, Yamano G, Sato H, Tahara Y, Ogura K, Nagashima K, Inagaki N.
  • Journal Title: Diabetes Volume: ahead of print
  • Peer Reviewed
• [Journal Article] Reduction of reactive oxygen species ameliorates metabolism-secretion coupling in islets of diabetic GK rats by suppressing lactate overproduction. (2013)
  • Author(s): Sasaki M, Fujimoto S, Sato Y, Nishi Y, Mukai E, Yamano G, Sato H, Tahara Y, Ogura K, Nagashima K, Inagaki N.
  • Journal Title: Diabetes Volume: ahead of print
  • Peer Reviewed
• [Journal Article] Role of endogenous ROS production in impaired metabolism-secretion coupling of diabetic pancreaticβcells (2011)
  • Author(s): Fujimoto S, Mukai E, Inagaki N
  • Journal Title: Prog Biophys Mol Biol Volume: 107 Issue: 2 Pages: 304-310
  • DOI: 10.1016/j.pbiomolbio.2011.07.013
  • Peer Reviewed
• [Journal Article] Three-diiensional ex vivo imaging and analysis of intraportal islet transplants (2011)
  • Author(s): Fujimoto H, Toyoda K, Okitsu T, Liu X, Mukai E, Zhuang X, Uemoto S, Mochizuki N, Inagaki N
  • Journal Title: Transplant International Volume: 24 Issue: 8 Pages: 839-844
  • DOI: 10.1111/j.1432-2277.2011.01271.x
  • Peer Reviewed
• [Journal Article] Role of mitochondrial phosphate carrier in metabolism-secretion coupling in rat insulinoma cell line INS-1 (2011)
  • Author(s): Nishi Y, Fujimoto S, Sasaki M, Mukai E, Sato H, Sato Y, Tahara Y, Nakamura Y, Inagaki N
  • Journal Title: Biochem J Volume: 435 Issue: 2 Pages: 421-430
  • DOI: 10.1042/bj20101708
  • Peer Reviewed
• [Journal Article] Role of Mitochondrial Phosphate Carrier in Metabolism-Secretion Coupling in Rat Insulinoma Cell Line INS-1. (2011)
  • Author(s): Nishi, Y., Fujimoto, S., Sasaki, M., Mukai, E., Sato, H., Sato, Y., Tahara, Y., Nakamura, Y., Inagaki, N.
  • Journal Title: Biochemical Journal Volume: 435(2) Pages: 421-430
  • Peer Reviewed
• [Journal Article] Role of endogenous ROS production in impaired metabolism-secretion coupling of diabetic pancreatic β cells. (2011)
  • Author(s): Fujimoto, S., Mukai, E., Inagaki, N.
  • Journal Title: Progress in Biophysics and Molecular Biology Volume: 107(2) Pages: 304-310
• [Presentation] VEGFシグナル阻害はSDTラットにおける膵島β細胞障害と糖尿病発症を抑制する (2013)
  • Author(s): 向英里、太田毅、河村治清、笹瀬智彦、李恩瑛、森田亜州華、稲垣暢也、岩永敏彦、三木隆司
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京
• [Presentation] SDTラットでは膵島内のVEGFシグナル亢進がβ細胞を障害し糖尿病を引き起こす (2013)
  • Author(s): 向英里、太田毅、河村治清、笹瀬智彦、李恩瑛、森田亜州華、稲垣暢也、岩永敏彦、三木隆司
  • Organizer: 第27回日本糖尿病・肥満動物学会年次学術集会
  • Place of Presentation: 東京
• [Presentation] Enhanced VEGF signaling in islets contributes to β-cell injury and consequential diabetes in SDT rats (2012)
  • Author(s): Mukai E, Ohta T, Kawamura H, Lee EY, Morita A, Inagaki N, Iwanaga T, Miki T.
  • Organizer: 9^<th> International Diabetes Federation Western Pacific Region Congress and 4^<th> Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Kyoto
• [Presentation] procyanidinsinprove glucose tolerance in diabetic ob/ob mice (2012)
  • Author(s): Ogura K, Nagashima K, Shoji T, Sato Y, Tahara Y, Yamano G, Sato H, Ogura M, Mukai E, Fujimoto S, Inagaki N. Apple
  • Organizer: 9^<th> International Diabetes Federation Western Pacific Region Congress and 4^<th> Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Kyoto
• [Presentation] Palmitate induces beta-cell dysfunction by activating NADPH oxidase through via the Src kinase signaling (2012)
  • Author(s): Sato Y, Fujimoto S, Mukai E, Sato S, Tahara Y, Ogura K, Yamano G, Ogura M, Nagashima K, Inagaki N.
  • Organizer: 9^<th> International Diabetes Federation Western Pacific Region Congress and 4^<th> Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Kyoto
• [Presentation] Development of 123I-labeled derivative targeting to GLP-1 receptor for insulinoma SPECT imaging (2012)
  • Author(s): Zhuang X, Toyoda K, Fujimoto H, Kimura H, Ogawa Y, Mukai E, Ueda M, Temma T, Hirai M, Takagi M, Kon A, Matsuda H, Ono M, Saji H, Inagaki N.
  • Organizer: 9^<th> International Diabetes Federation Western Pacific Region Congress and 4^<th> Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Kyoto
• [Presentation] Src regulates insulin secretion by modulating glucokinase activity in INS-1 cells (2012)
  • Author(s): Sato S, Fujimoto S, Nagashima K, Mukai E, Ogura M, Sato Y, Yamano G, Tahara Y, Ogura K, Sugizaki K, Inagaki N.
  • Organizer: 9^<th> International Diabetes Federation Western Pacific Region Congress and 4^<th> Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Kyoto
• [Presentation] Development of non-invasive PET probe for quantifying pancreatic b-cell mass usingfluorine-18-labeled exendin-4 (2012)
  • Author(s): Fujimoto H, Toyoda K, Kimura H, Ogawa Y, Mukai E, Zhuang X, Ueda M, Temma T, Hirai M, Matsuda H, Saji H, Inagaki N.
  • Organizer: 9^<th> International Diabetes Federation Western Pacific Region Congress and 4^<th> Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Kyoto
• [Presentation] 活性酸素種抑制によるWarburg効果改善を介するGKラットインスリン分泌障害改善効果-癌代謝類似代謝障害制御の重要性- (2012)
  • Author(s): 佐々木真弓、藤本新平、西勇一、向英里、佐藤雄一、佐藤広規、田原裕美子、小倉かさね、山野言、長嶋一昭、稲垣暢也
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
• [Presentation] 活性酸素種抑制によるWarburg効果改善を介するGKラットインスリン分泌障害改善効果－癌代謝類似代謝障害制御の重要性－ (2012)
  • Author(s): 佐々木真弓、藤本新平、西勇一、向英里、佐藤雄一、佐藤広規、田原裕美子、小倉かさね、山野言、長嶋一昭、稲垣暢也
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
• [Presentation] Enhanced VEGF signaling in islets contributes to b-cell injury and consequential diabetes in SDT rats. (2012)
  • Author(s): Mukai E, Ohta T, Kawamura H, Lee EY, Morita A, Inagaki N, Iwanaga T, Miki T.
  • Organizer: 9th International Diabetes Federation Western Pacific Region Congress and 4th Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Kyoto
• [Presentation] Apple procyanidinsinprove glucose tolerance in diabetic ob/ob mice. (2012)
  • Author(s): Ogura K, Nagashima K, Shoji T, Sato Y, Tahara Y, Yamano G, Sato H, Ogura M, Mukai E, Fujimoto S, Inagaki N.
  • Organizer: 9th International Diabetes Federation Western Pacific Region Congress and 4th Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Kyoto
• [Presentation] Palmitate induces beta-cell dysfunction by activating NADPH oxidase through via the Src kinase signaling. (2012)
  • Author(s): Sato Y, Fujimoto S, Mukai E, Sato S, Tahara Y, Ogura K, Yamano G, Ogura M, Nagashima K, Inagaki N.
  • Organizer: 9th International Diabetes Federation Western Pacific Region Congress and 4th Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Kyoto
• [Presentation] Development of 123I-labeled derivative targeting to GLP-1 receptor for insulinoma SPECT imaging. (2012)
  • Author(s): Zhuang X, Toyoda K, Fujimoto H, Kimura H, Ogawa Y, Mukai E, Ueda M, Temma T, Hirai M, Takagi M, Kon A, Matsuda H, Ono M, Saji H, Inagaki N.
  • Organizer: 9th International Diabetes Federation Western Pacific Region Congress and 4th Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Kyoto
• [Presentation] Src regulates insulin secretion by modulating glucokinase activity in INS-1 cells. (2012)
  • Author(s): Sato S, Fujimoto S, Nagashima K, Mukai E, Ogura M, Sato Y, Yamano G, Tahara Y, Ogura K, Sugizaki K, Inagaki N.
  • Organizer: 9th International Diabetes Federation Western Pacific Region Congress and 4th Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Kyoto
• [Presentation] Development of non-invasive PET probe for quantifying pancreatic b–cell mass using fluorine-18-labeled exendin-4. (2012)
  • Author(s): Fujimoto H, Toyoda K, Kimura H, Ogawa Y, Mukai E, Zhuang X, Ueda M, Temma T, Hirai M, Matsuda H, Saji H, Inagaki N.
  • Organizer: 9th International Diabetes Federation Western Pacific Region Congress and 4th Scientific Meeting of the Asian Association for the Study of Diabetes
  • Place of Presentation: Kyoto
• [Presentation] Exendin-4はGKラット膵島においてEpac依存性にSrc活性を抑制することによりROS産生を減少させる (2011)
  • Author(s): 向英里、藤本新平、佐藤広規、小根山千歳、佐藤雄一、佐々木真弓、西勇一、岡田雅人、稲垣暢也
  • Organizer: 第25回日本糖尿病・肥満動物学会年次学術集会
  • Place of Presentation: 東京
• [Presentation] eNOS欠損マウスを用いたメトホルミンによる肝糖新性抑制機序および血糖低下作用機序の解明 (2011)
  • Author(s): 藤田義人、細川雅也、藤本新平、Abudukadier Abulizi、小原章央、向英里、小倉雅仁、中村靖彦、長嶋一昭、清野裕、稲垣暢也
  • Organizer: 第25回日本糖尿病・肥満動物学会年次学術集会
  • Place of Presentation: 東京
• [Presentation] Role of Mitochondrial Phosphate Carrier in Metabolism-Secretion Coupling in Rat Insulinoma Cell Line INS-1 (2011)
  • Author(s): Nishi Y, Fujimoto S, Sasaki M, Mukai E, Sato H, Sato Y, Tahara Y, Nakamura Y, Inagaki N.
  • Organizer: 16^<th> Japan-Korea Symposium on Diabetes Mellitus
  • Place of Presentation: Tokyo
• [Presentation] Development of non-invasive PET probe for quantifying pancreatic β-cell mass using fluorine-18-labeled exendin-4 (2011)
  • Author(s): Toyoda K, Kimura H, Fujimoto H, Zhuang X, Mukai E, Ogawa Y, Hirao K, Matsuda H, Kawashima H, Ueda M, Temma T, Saji H, Inagaki N.
  • Organizer: 71th Scientific Sessions of AmericanDiabetes Association
  • Place of Presentation: San Diego, USA
• [Presentation] Non-invasive SPECT imaging of pancreatic islets targeting glucagon-like peptide-1 receptors (2011)
  • Author(s): Fujimoto H, Toyoda K, Kimura H, Ogawa Y, Mukai E, Zhuang X, Kawashima H, Matsuda H, Hirao K, Saji H, Inagaki N.
  • Organizer: 71th Scientific Sessions of American Diabetes Association
  • Place of Presentation: San Diego, USA
• [Presentation] Role of endogenos ROS production in metabolism-secretion coupling of pancreatic β-cells (2011)
  • Author(s): Shimpei Fujimoto, Eri Mukai, Nobuya Inagaki
  • Organizer: 第54回日本糖尿病学 会年次学術集会
  • Place of Presentation: 札幌
• [Presentation] GLP-1受容体を標的とする非侵襲的イメージングのためのPET用プローブの開発 (2011)
  • Author(s): 豊田健太郎、木村寛之、藤本裕之、小川祐、向英里、庄暁桐、河嶋秀和、平尾佳、松田洋和、佐治英郎、稲垣暢也
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
• [Presentation] GLP-1受容体を標的とするSPECT用膵島イメージングプローブの開発 (2011)
  • Author(s): 藤本裕之、豊田健太郎、木村寛之、小川祐、向英里、庄暁桐、河嶋秀和、平尾佳、松田洋和、佐治英郎、稲垣暢也
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
• [Presentation] マウス同系膵島移植において、ONO-1301はPGI2受容体を介する膵β細胞保護作用によって膵島の生着を改善する (2011)
  • Author(s): 庄暁桐、豊田健太郎、劉喜宝、向英里、藤本裕之、酒井芳紀、、古家敷智之、松本邦夫、成宮周、稲垣暢也
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
• [Presentation] 膵β細胞の代謝分泌連関におけるミトコンドリアリン酸キャリアの役割 (2011)
  • Author(s): 西勇一、藤本新平、佐々木真弓、向英里、佐藤広規、佐藤雄一、田原裕美子、中村靖彦、稲垣暢也
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
• [Presentation] 受賞講演 Role of endogenos ROS production in metabolism-secretion coupling of pancreatic b-cells. (2011)
  • Author(s): Fujimoto, S., Mukai, E., Inagaki, N.
  • Organizer: 第54回 日本糖尿病学会年次学術集会(招待講演)
  • Place of Presentation: 札幌
• [Presentation] GLP-1受容体を標的とする非侵襲的イメージングのためのPET用プローブの開発 (2011)
  • Author(s): 豊田健太郎、木村寛之、藤本裕之、小川祐、向英里、庄暁桐、河嶋秀和、平尾佳、松田洋和、佐治英郎、稲垣暢也
  • Organizer: 第54回 日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
• [Presentation] 膵β細胞の代謝分泌連関におけるミトコンドリアリン酸キャリアの役割 (2011)
  • Author(s): 西勇一、藤本新平、佐々木真弓、向英里、佐藤広規、佐藤雄一、田原裕美子、中村靖彦、稲垣暢也
  • Organizer: 第54回 日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
• [Presentation] GLP-1受容体を標的とするSPECT用膵島イメージングプローブの開発 (2011)
  • Author(s): 藤本裕之、豊田健太郎、木村寛之、小川祐、向英里、庄暁桐、河嶋秀和、平尾佳、松田洋和、佐治英郎、稲垣暢也
  • Organizer: 第54回 日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
• [Presentation] マウス同系膵島移植において、ONO-1301はPGI2受容体を介する膵β細胞保護作用によって膵島の生着を改善する (2011)
  • Author(s): 庄暁桐、豊田健太郎、劉喜宝、向英里、藤本裕之、酒井芳紀、、古家敷智之、松本邦夫、成宮周、稲垣暢也
  • Organizer: 第54回 日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
• [Presentation] Development of non-invasive PET probe for quantifying pancreatic b-cell mass using fluorine-18-labeled exendin-4. (2011)
  • Author(s): Toyoda, K., Kimura, H., Fujimoto, H., Zhuang, X., Mukai, E., Ogawa, Y., Hirao, K., Matsuda, H., Kawashima, H., Ueda. M., Temma, T., Saji, H., Inagaki, N.
  • Organizer: 71th Scientific Sessions of American Diabetes Association
  • Place of Presentation: San Diego
• [Presentation] Non-invasive SPECT imaging of pancreatic islets targeting glucagon-like peptide-1 receptors. (2011)
  • Author(s): Fujimoto, H., Toyoda, K., Kimura, H., Ogawa, Y., Mukai, E., Zhuang, X., Kawashima, H., Matsuda, H., Hirao, K., Saji, H., Inagaki, N.
  • Organizer: 71th Scientific Sessions of American Diabetes Association
  • Place of Presentation: San Diego
• [Presentation] Role of Mitochondrial Phosphate Carrier in Metabolism-Secretion Coupling in Rat Insulinoma Cell Line INS-1. (2011)
  • Author(s): Nishi, Y., Fujimoto, S. , Sasaki, M., Mukai, E., Sato, H., Sato, Y., Tahara, Y., Nakamura, Y., Inagaki, N.
  • Organizer: 16th Japan-Korea Symposium on Diabetes Mellitus
  • Place of Presentation: Tokyo
• [Presentation] Exendin-4はGKラット膵島においてEpac依存性にSrc活性を抑制することによりROS産生を減少させる (2011)
  • Author(s): 向英里、藤本新平、佐藤広規、小根山千歳、佐藤雄一、佐々木真弓、西勇一、岡田雅人、稲垣暢也
  • Organizer: 第25回 日本糖尿病・肥満動物学会年次学術集会
  • Place of Presentation: 東京
• [Presentation] eNOS欠損マウスを用いたメトホルミンによる肝糖新性抑制機序および血糖低下作用機序の解明 (2011)
  • Author(s): 藤田義人、細川雅也、藤本新平、Abudukadier Abulizi、小原章央、向英里、小倉雅仁、中村靖彦、長嶋一昭、清野裕、稲垣暢也
  • Organizer: 第25回 日本糖尿病・肥満動物学会年次学術集会
  • Place of Presentation: 東京
• [Book] 低血糖についての新しい知見1.インクレチン関連薬とスルホニル尿素薬のによる低血糖 (2011)
  • Author(s): 向英里、稲垣暢也
  • Publisher: 糖尿病学会誌、(社)日本糖尿病学会
• [Book] Clinical Note DPP-4阻害薬とSU薬併用による低血、Diabetes Journal(糖尿病と代謝) (2011)
  • Author(s): 向英里、稲垣暢也
  • Publisher: (株)協和企画
• [Book] III-5.インクレチン関連薬とSU薬併用時における重症低血糖発症メカニズムとその対策 (2011)
  • Author(s): 向英里、藤本新平、稲垣暢也
  • Publisher: 日本臨床、(株)日本臨床社
• [Book] 日本臨床，69-5 (2011)
  • Author(s): 向英里、藤本新平、稲垣暢也
  • Total Pages: 5
  • Publisher: インクレチン関連薬とSU薬併用時における重症低血糖発症メカニズムとその対策
• [Book] Diabetes Journal（糖尿病と代謝），39-1 (2011)
  • Author(s): 向英里、稲垣暢也
  • Total Pages: 5
  • Publisher: DPP-4阻害薬とSU薬併用による低血糖
• [Book] 糖尿病，54-12 (2011)
  • Author(s): 向英里、稲垣暢也
  • Total Pages: 3
  • Publisher: 「低血糖についての新しい知見」１．インクレチン関連薬とスルホニル尿素薬のによる低血糖