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Elucidation of molecular mechanisms on macrophage infiltration into pancreatic islets in type 2 diabetes and challenging trial to establish its preventive strategy.

Research Project

Project/Area Number 25461363
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionKyorin University

Principal Investigator

Ishida Hitoshi  杏林大学, 医学部, 教授 (80212893)

Co-Investigator(Kenkyū-buntansha) INUKAI Koichi  杏林大学, 医学部, 准教授 (20333007)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords2型糖尿病 / マクロファージ / 膵β細胞 / 脂肪細胞 / MCP-1 / 内因性酸化ストレス / Astaxanthin / JNK経路 / 2型糖尿病 / 脂肪脂肪 / VEGF / PI3K依存性経路
Outline of Final Research Achievements

We analyzed the influence of antioxidant astaxanthin on monocyte chemoattractant protein-1 (MCP-1), a key factor on free fatty acids-induced chronic inflammation, by using mouse insulinoma (MIN6) cells long-term treated with high concentration of palmitate. While palmitate significantly increased endogenous oxidative stress and enhanced MCP-1 secretion in MIN6 cells, astaxanthin as well as SP600125, a JNK-specific inhibitor, clearly reduced this enhanced MCP-1. Furthermore, astaxanthin attenuated JNK phosphorylation, and also diminished endoplasmic reticulum stress enhanced by palmitate.
Taken together, astaxanthin can suppress MCP-1 release, which is up-regulated by palmitate, through the inactivity of JNK pathways on MIN6 cells. The results of this study raise the possibility that astaxanthin would become a new preventive tool for the progression of β cell dysfunction observed in type 2 diabetes with clinical dyslipidemia.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (29 results)

All 2016 2015 2014 2013 Other

All Journal Article (10 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (14 results) (of which Invited: 2 results) Book (4 results) Remarks (1 results)

  • [Journal Article] The association between impaired proinsulin processing and type 2 diabetes mellitus in non-obese Japanese individuals2015

    • Author(s)
      H.Katsuta, S.Ozawa, K.Suzuki, K.Takahashi, T.Tanaka, Y.Sumitani, S.Nishida, T.Kondo, T.Hosaka, and H.Ishida.
    • Journal Title

      Endocrine Journal

      Volume: 62 Issue: 6 Pages: 485-492

    • DOI

      10.1507/endocrj.EJ14-0611

    • NAID

      130005085772

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Habitual exercise training acts as a physiological stimulator for constant activation of lipolytic enzymes in primary white adipocytes.2015

    • Author(s)
      J.Ogasawara, T.Izawa, T.Sakurai, K.Shirota, Y.Ishibashi, Y.Ohira, H.Ishida, H.Ohno, and T.Kizaki.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 464 Pages: 348-353

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ghrelin augments the expressions and secretions of proinflammatory adipokines, VEGF120 and MCP-1, in differentiated 3T3-L1 adipocytes.2015

    • Author(s)
      A. Kitahara, K. Takahashi, R. Moriya, H. Onuma, K. Handa, Y. Sumitani, T. Tanaka, H. Katsuta, S. Nishida, T. Sakurai, K. Inukai, H. Ohno, and H. Ishida.
    • Journal Title

      J Cell Physiol

      Volume: 230 Issue: 1 Pages: 199-209

    • DOI

      10.1002/jcp.24699

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparisons of microRNA expression profiles in vitreous humor between eyes with macular hole and eyes with proliferative diabetic retinopathy.2015

    • Author(s)
      K. Hirota, H. Keino, M. Inoue, H. Ishida, and A. Hirakata
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol

      Volume: 253 Issue: 3 Pages: 335-342

    • DOI

      10.1007/s00417-014-2692-5

    • Related Report
      2014 Research-status Report
  • [Journal Article] Estimated proinsulin processing activity of prohormone convertase (PC) 1/3 rather than PC2 is decreased in pancreatic β-cells of type 2 diabetic patients.2014

    • Author(s)
      S.Ozawa*, H.Katsuta*, K.Suzuki, K.Takahashi, T.Tanaka, Y.Sumitani, S.Nishida, K.Yoshimoto, and H.Ishida. (*equally contributed)
    • Journal Title

      Endocr J

      Volume: 61(6) Pages: 607-614

    • NAID

      130004770451

    • Related Report
      2014 Research-status Report
  • [Journal Article] Long-term low carbohydrate diet leads to deleterious metabolic manifestations in diabetic mice.2014

    • Author(s)
      Handa K, Inukai K, Onuma H, Kudo A, Nakagawa F, Tsuruga K, Kitahara A, Moriya R, Takahashi K, Sumitani Y, Hosaka T, Kawakami H, Oyadomari S, Ishida H
    • Journal Title

      PLoS One

      Volume: 9 Issue: 8 Pages: 104948-104948

    • DOI

      10.1371/journal.pone.0104948

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Effects of long-term monotherapy with glimepiride vs glibenclamide on glycemic control and macrovascular events in Japanese type 2 diabetic patients.2014

    • Author(s)
      H.Onuma, K.Inukai, M.Watanabe, Y.Sumitani, T.Hosaka, and H.Ishida.
    • Journal Title

      J Diabetes Mellitus

      Volume: 4(1) Issue: 01 Pages: 33-37

    • DOI

      10.4236/jdm.2014.41006

    • Related Report
      2014 Research-status Report 2013 Research-status Report
  • [Journal Article] Enzyme-treated asparagus officinalis extract shows neuroprotective effects and attenuates cognitive impairment in senescence-accelerated mice.2014

    • Author(s)
      T. Sakurai, T. Ito, K.Wakame, K. Kitadate, T.Arai, J. Ogasawara, T. Kizaki, S.Sato, Y.Ishibashi,T.Fujiwara, K.Akagawa H. Ishida, and H. Ohno.
    • Journal Title

      Natural Product Commun

      Volume: 9(1) Pages: 101-106

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of PI3K-dependent pathways in the increased VEGF120 release from osteoblastic cells preloaded with palmitate.2014

    • Author(s)
      R. Moriya, K. Takahashi, A. Kitahara, H. Onuma, K. Handa, Y. Sumitani, T. Tanaka, H.Katsuta, S. Nishida, E. Itagaki, K. Inukai, and H. Ishida.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 445 Issue: 2 Pages: 275-281

    • DOI

      10.1016/j.bbrc.2014.01.120

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Endogenous oxidative stress, but not ER stress, induces hypoxia-independent VEGF120 release through PI3K-dependent pathways in 3T3-L1 adipocytes.2013

    • Author(s)
      Takahashi, K., et al.
    • Journal Title

      Obesity

      Volume: 21 Issue: 8 Pages: 1625-1634

    • DOI

      10.1002/oby.20206

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] パルミチン酸負荷による骨芽細胞からのVEGF120分泌増大にはPI3K依存性の経路が関与している可能性がある.2015

    • Author(s)
      森谷理恵,高橋和人,北原敦子,炭谷由計,小沼裕寿,田中利明,勝田秀紀,西田進,近藤琢磨,保坂利男,犬飼浩一,石田均
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 膵β細胞の酸化ストレス下におけるオートファジー機構の意義とアスタキサンチンの保護作用の検討.2015

    • Author(s)
      北原敦子,近藤琢磨,高橋和人,村嶋俊隆,森田奈瑠,小沼裕寿,炭谷由計,田中利明,勝田秀紀,保坂利男,犬飼浩一,石田均
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 2型糖尿病における骨代謝異常の増悪・進展機構の解明とそれに対する温熱処理の影響の解析.2015

    • Author(s)
      高橋和人,森谷理恵,北原敦子,半田桂子,小沼裕寿,炭谷由計,田中利明,勝田秀紀,西田進,近藤琢磨,保坂利男,犬飼浩一,石田均
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 2型糖尿病治療別にみるプロインスリンプロセシング機構の回復.2015

    • Author(s)
      勝田秀紀,近藤琢磨,石本麻衣,森田奈瑠,村嶋俊隆,小沼裕寿,森谷理恵,高橋和人,田中利明,鈴木清,保坂利男,犬飼浩一,石田均
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 日本人のための糖尿病食事療法.2015

    • Author(s)
      石田均
    • Organizer
      第12回日本内科学会総会
    • Place of Presentation
      京都
    • Year and Date
      2015-04-10
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] VEGF120 secretion from palmitate-preloaded osteoblastic cells is enhanced through the activation of PI3K-dependent pathways.2014

    • Author(s)
      Moriya R, Takahashi K, Kitahara A, Onuma H, Handa K, Sumitani Y, Tanaka T, Katsuta H, Nishida S, Itagaki E, Inukai K, Ishida H
    • Organizer
      The American Diabetes Association's 73nd Scientific Sessions,
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2014-06-13 – 2014-06-17
    • Related Report
      2014 Research-status Report
  • [Presentation] Direct action of ghrelin enhance the secretions of proinflammatory adipokines from mature 3T3-L1 adipcocytes in vitro.2014

    • Author(s)
      Kitahara A, Takahashi K, Moriya R, Onuma H, Handa K, Sumitani Y, Tanaka T, Katsuta H, Nishida S, Sakurai T, Inukai K, Ohno H, Ishida H
    • Organizer
      The American Diabetes Association's 73nd Scientific Sessions,
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2014-06-13 – 2014-06-17
    • Related Report
      2014 Research-status Report
  • [Presentation] 膵β細胞保護効果に対するアスタキサンチンの細胞内作用機構に関する検討―ケモカインのMCP-1の分泌動態への影響―.2014

    • Author(s)
      北原敦子,高橋和人,森谷理恵,小沼裕寿,半田桂子,森田奈瑠,石本麻衣,炭谷由計,田中利明,勝田秀紀,西田進,犬飼浩一,石田均
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] 糖尿病での骨代謝異常における基盤病態の解明とそれに対する温熱処理の影響の検討.2014

    • Author(s)
      高橋和人,森田理恵,北原敦子,半田桂子,小沼裕寿,村嶋俊隆,炭谷由計,田中利明,勝田秀紀,西田進,犬飼浩一,石田均
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] 骨芽細胞からのサイトカイン分泌に及ぼす飽和脂肪酸の影響とその細胞内シグナル伝達経路に関する検討2014

    • Author(s)
      森田理恵,高橋和人,北原敦子,小沼裕寿,半田桂子,炭谷由計,田中利明,勝田秀紀,西田進,板垣英二,犬飼浩一,石田均
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] グレリンによる脂肪細胞からのアディポカイン分泌制御機構―MCP-1ならびにVEGF120分泌の促進作用とその分子機構の解明―2013

    • Author(s)
      北原敦子,高橋和人,五林可織,半田桂子,森谷理恵,小沼裕寿,炭谷由計,田中利明,勝田秀紀,西田進,板垣英二,犬飼浩一,石田均
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] 肥大化脂肪細胞からの完全分泌型VEGF120の低酸素非依存的分泌制御機構の解明2013

    • Author(s)
      高橋和人,北原敦子,森谷理恵,五林可織,半田桂子,小沼裕寿,炭谷由計,田中利明,勝田秀紀,西田進,犬飼浩一,石田均
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] 飽和脂肪酸が及ぼす骨芽細胞機能への影響とその分子機構の解析2013

    • Author(s)
      森谷理恵,高橋和人,北原敦子,五林可織,半田桂子,小沼裕寿,炭谷由計,田中利明,勝田秀紀,西田進,板垣英二,犬飼浩一,石田均
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] 日本人の糖尿病食事療法に求められるもの2013

    • Author(s)
      石田均
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
    • Invited
  • [Book] 人体の構造と機能及び疾病の成り立ち22016

    • Author(s)
      志村二三夫、石田 均
    • Total Pages
      204
    • Publisher
      建帛社
    • Related Report
      2015 Annual Research Report
  • [Book] 人体の構造と機能及び2015

    • Author(s)
      志村二三夫、石田 均
    • Total Pages
      283
    • Publisher
      建帛社
    • Related Report
      2014 Research-status Report
  • [Book] 人体の構造と機能及び疫病の成り立ち 総論.改訂第2版2013

    • Author(s)
      香川靖雄、近藤和雄、石田均、門脇孝
    • Total Pages
      341
    • Publisher
      南江堂
    • Related Report
      2013 Research-status Report
  • [Book] 人体の構造と機能及び疫病の成り立ち 各論.改訂第2版2013

    • Author(s)
      香川靖雄、近藤和雄、石田均、門脇孝
    • Total Pages
      591
    • Publisher
      南江堂
    • Related Report
      2013 Research-status Report
  • [Remarks] 杏林大学第3内科学教室ウェブページ

    • URL

      http://www.kyorin-u.ac.jp/univ/graduate/medicine/education/departments/intern-med3/

    • Related Report
      2015 Annual Research Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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