Elucidation of involved mechanisms for macrophage infiltration into pancreatic islets and of its role on the occurrence of type 2 diabetes.

• Project/Area Number: 22590993
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kyorin University
• Principal Investigator: ISHIDA Hitoshi 杏林大学, 医学部, 教授 (80212893)
• Co-Investigator(Kenkyū-buntansha): NAGAMATSU Shinya 杏林大学, 医学部, 教授 (80231489) ; YOSHIMOTO Katsuhiko 杏林大学, 医学部, 講師 (20271257) ; INUKAI Kouichi 杏林大学, 医学部, 准教授 (20333007)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 2型糖尿病 / 膵ラ氏島 / マクロファージ / サイトカイン / 熱ショック蛋白 / 膵β細胞 / 脂肪細胞 / インスリン分泌 / MCP-1 / VEGF / 酸化ストレス / アンカップリング

Research Abstract

The JNK and IκB- dependent pathways were deduced, at least in part, as common mechanisms for the increased release of MCP-1 from pancreatic MIN6βcells and 3T3L1 adipocytes under diabetic conditions, leading to the enhancement of macrophage infiltration into pancreatic islets and adipose tissues, respectively. In addition, we explored the cytoprotective mechanism to reduce MCP-1 release from 3T3L1 adipocytes, and it was found that the induction of metabolic uncoupling in mitochondria to activate the AMP-activated protein kinase and also of heat shock protein 72 at 41℃could be important in these cells for the reduction of MCP-1 release.

Research Products

• [Journal Article] Induction of mitochondrial uncoupling enhances VEGF120 but reduces MCP-1 release in mature 3T3-L1 adipocytes: possible regulatory mechanism through endogenous ER stress and AMPK-related pathways. (2012)
  • Author(s): K. Miyokawa-Gorin *, K. Takahashi *, K. Handa, A. Kitahara, Y. Sumitani, H. Katsuta, T. Tanaka, S. Nishida, K. Yoshimoto, H. Ohno, and H. Ishida.(*equally contributed)
  • Journal Title: Biochem Biophys Res Commun Volume: 419 Pages: 200-205
• [Journal Article] Higher levels of ATGL are associated with exercise-induced enhancement of lipolysis in rat epididymal adipocytes (2012)
  • Author(s): J. Ogasawara, T. Sakurai, T. Kizaki, Y. Ishibashi, T. Izawa, Y. Sumitani, H. Ishida, Z. Radak, S. Haga, and H. Ohno
  • Journal Title: PLoS ONE Volume: 7(7)
• [Journal Article] Higher levels of ATGL are associated with exercise-induced enhancement of lipolysis in rat epididymal adipocytes. (2012)
  • Author(s): 小笠原準悦
  • Journal Title: PLoS ONE Volume: 7(7) Issue: 7 Pages: e40876-e40876
  • DOI: 10.1371/journal.pone.0040876
  • Peer Reviewed
• [Journal Article] Preventive and improvement effects of exercise training and supplement intake in white adipose tissues on obesity and lifestyle-related diseases (2012)
  • Author(s): Sakurai, T., Ogasawara, J., Kizaki, Takahashi, K., Ishida, H., Miyazaki, H., Saitoh, D., Haga, S., Izawa, T. & Ohno, H.
  • Journal Title: Environ. Health Prev. Med Volume: 17(in press) Issue: 5 Pages: 348-356
  • DOI: 10.1007/s12199-012-0271-0
  • NAID: 10031120507
  • Peer Reviewed
• [Journal Article] Induction of mitochondrial uncoupling enhances VEGF_<120> but reduces MCP-1 release in mature 3T3-L1 adipocytes : Possible regulatory mechanism through endogenous ER stress and AMPK-related pathways (2012)
  • Author(s): Miyokawa-Gorin, K., Takahashi, K., Handa, K., Kitahara, A., Sumitani, Y., Katsuta, H., Tanaka, T., Nishida, S., Yoshimoto, K., Ohno, H. & Ishida, H
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 419 Issue: 2 Pages: 200205-200205
  • DOI: 10.1016/j.bbrc.2012.01.145
  • Peer Reviewed
• [Journal Article] Hormone-sensitive lipase is critical mediators of acute exercise-induced regulation of lipolysis in rat adipocytes (2010)
  • Author(s): J. Ogasawara, S. Nomura, N. Rahman, T. Sakurai, T. Kizaki, T. Izawa, H. Ishida, S. Haga and H. Ohno.
  • Journal Title: Biochem Biophys Res Commun Volume: 400 Pages: 134-139
• [Journal Article] Oligonol, an oligomerized lychee fruit-derived polyphenol, activates the Ras/Raf-1/MEK1/2 cascade independent of the IL-6 signaling pathway in rat primary adipocytes. (2010)
  • Author(s): J. Ogasawara, K. Kitadate, H. Nishioka, H. Fujii, T. Sakurai, T. Kizaki, T. Izawa, H. Ishida, H. Tanno, and H. Ohno
  • Journal Title: Biochem Biophys Res Commun Volume: 402 Pages: 554-559
• [Journal Article] Effect of exercise training on adipogenesis of stromal-vascular fraction cells in rat epididymal white adipose tissue (2010)
  • Author(s): T. Sakurai, S. Endo, D. Hatano, J. Ogasawara, T. Kizaki, S. Oh-ishi, T. Izawa, H. Ishida, and H. Ohno
  • Journal Title: Acta Physiol Volume: 200 Pages: 325-338
• [Journal Article] Oligomerized grape seed polyphenols attenuate inflammatory changes due to antioxidative properties in co-culture of adipocytes and macrophages. (2010)
  • Author(s): T.Sakurai, H.Ishida, et al.
  • Journal Title: J Nutr Biochem Volume: 23 Pages: 1626-1633
  • Peer Reviewed
• [Journal Article] Oligonol, an oligomerized lychee fruit-derived polyphenol, activates the Ras/Raf-1/MEK 112 cascade independent of the IL-6 signaling pathway in rat primary adipocytes. (2010)
  • Author(s): J.Ogasawara, H.Ishida, et al
  • Journal Title: Biochem Biophys Res Commun Volume: 402 Pages: 554-559
  • Peer Reviewed
• [Journal Article] Effect of exercise training on adipogenesis of stromal-vascular fraction cells in rat epididymal white adipose tissue. (2010)
  • Author(s): T.Sakurai, H.Ishida, et al.
  • Journal Title: Acta Physiol Volume: 200 Pages: 325-338
  • Peer Reviewed
• [Journal Article] Endogenous oxidative stress, but not ER stress, induces hypoxia-independent VEGF120 release through PI3K-dependent pathways in 3T3-L1 adipocytes.
  • Author(s): K. Takahashi, K. Miyokawa-Gorin, K. Handa, A. Kitahara, R. Moriya, H. Onuma, Y. Sumitani, T. Tanaka, H. Katsuta, S. Nishida, K. Yoshimoto, H. Ohno and H. Ishida.
  • Journal Title: Obesity Volume: (in press)
• [Presentation] 脂肪細胞からの炎症関連アディポカイン分泌における温熱処理の影響とその意義. (2012)
  • 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33回日本肥満学会
  • Place of Presentation: 京都
  • Year and Date: 2012-10-11
• [Presentation] 温熱処理によるHSP72発現の増強と脂肪細胞由来炎症関連アディポカインの分泌動態の変化について (2012)
  • Author(s): 高橋和人,北原敦子,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,吉元勝彦,石田均
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
• [Presentation] 温熱処理によるHSP72発現の増強と脂肪細胞由来炎症関連アディポカインの分泌動態の変化について． (2012)
  • Author(s): 高橋和人
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
• [Presentation] 脂肪細胞からの炎症関連アディポカイン分泌における温熱処理の影響とその意義． (2012)
  • Author(s): 高橋和人
  • Organizer: 第33回日本肥満学会
  • Place of Presentation: 京都
• [Presentation] 脂肪細胞からのアディポネクチン分泌に及ぼすmitochondrial uncoupling の影響とその制御機構に関わる細胞内情報伝達系の検討 (2011)
  • Author(s): 五林可織,高橋和人,半田桂子,北原敦子,炭谷由計,田中利明,勝田秀紀,西田 進,吉元勝彦,板垣英二,石田 均
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
• [Presentation] 脂肪細胞からのアディポカイン分泌に及ぼすmitochondrial uncouplingの影響とその制御機構に関わる細胞内情報伝達系の検討 (2011)
  • Author(s): 高橋和人、五林可織, ら
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌市
• [Presentation] 脂肪細胞のミトコンドリア内でのmetabolic couplingが細胞機能に果たす役割について (2010)
  • Author(s): 三代川可織,高橋和人,半田桂子,黒川三知子,森谷理恵,下山達宏,田中利明,勝田秀紀,山口真哉,吉元勝彦,石田均
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山
• [Presentation] 脂肪細胞のミトコンドリア内でのmetabolic couplingが細胞機能に果たす役割について (2010)
  • Author(s): 三代川可織、高橋和人, ら
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山市