Elucidation of involved mechanisms impaired for insulin secretion due to oxidative stress and macrophages in pancreatic islets of type 2 diabetes.

• Project/Area Number: 19591065
• 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 Kyorin University, 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)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 2型糖尿病 / インスリン分泌 / 酸化ストレス / マクロファージ / 膵β細胞 / 脂肪細胞 / MCP-1

Research Abstract

The increased release of MCP-1 was observed from pancreatic MIN6 β cells under diabetic conditions, leading to the enhancement of macrophage infiltration into pancreatic islets. And increased endogenous oxidative stress in β cells could be related to its underlying mechanism. In addition, the release of MCP-1 and VEGF was also found to be increased from 3T3L1 adipocytes. The enhancement of endogenous oxidative stress was similarly speculated to be the pathogenic mechanism of their increased secretion, and in terms of released MCP-1, we deduce that the IkB- dependent pathway is, at lease in part, important as a common distal signaling in both pancreatic β cells and adipocytes.

Research Products

• [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, K. Kitadate, H. Nishioka, H. Fujii, T. Kizaki, Y. Kondoh, T. Izawa, H. Ishida, Z. Radak, H. Ohno
  • Journal Title: J Nutr Biochem 23 Pages: 1626-1633
• [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 23 Pages: 1626-1633
  • Peer Reviewed
• [Journal Article] Oligonol, a new lychee fruit-derived low-molecular form of polyphenol, enhances lipolysis in primary rat adipocytes through activation of the ERK1/2 pathway. (2009)
  • Author(s): J. Ogasawara, K. Kitadate, H. Nishioka, H. Fujii, T. Sakurai, T. Kizaki, T. Izawa, H. Ishida, H. Ohno
  • Journal Title: Phytotherapy Res 21 Pages: 47-54
• [Journal Article] Exercise training decreases expression of inflammation-related adipokines through reduction of oxidative stress in rat white adipose tissue. (2009)
  • Author(s): T. Sakurai, T. Izawa, T. Kizaki, J. Ogasawara, K. Shirato, K. Imaizumi, K. Takahashi, H. Ishida, H. Ohno
  • Journal Title: Biochem Biophys Res Commun 379 Pages: 605-609
• [Journal Article] Exercise training decreases expression of inflammation-related adipokines through reduction of oxidative stress in rat white adipose tissue. (2009)
  • Author(s): T.Sakurai, H.Ishida, et al.
  • Journal Title: Biochem Biophys Res Commun 379 Pages: 605-609
  • Peer Reviewed
• [Journal Article] Oligonol, a new lychee fruit-derived low-molecular form of polyphenol, enhances lipolysis in primary rat adipocytes through activation of the ERK1/2 pathway. (2009)
  • Author(s): J.Ogasawara, H.Ishida, et al.
  • Journal Title: Phytotherapy Res 21 Pages: 47-54
  • Peer Reviewed
• [Journal Article] Exercise training decreases expression of inflammation-related adipokines through reduction of oxidative stress in rat white adipose tissue. (2009)
  • Author(s): T. Sakurai, H. Ishida, et al.
  • Journal Title: Biochem Biophys Res Commun 379 Pages: 605-609
  • Peer Reviewed
• [Journal Article] Enhanced release of monocyte chemoattractant protein-1 (MCP-1) by high glucose and free fatty acid and its underlying mechanism in MIN6 Bcells. (2009)
  • Author(s): H. Seki, H. Ishida, et al.
  • Journal Title: J Kyorin Med Soc (in press)
  • Peer Reviewed
• [Journal Article] Enhanced release of monocyte chemoattractant protein-1 (MCP-1) by high glucose and free fatty acid and its underlying mechanism in MIN6βcells. (2008)
  • Author(s): H. Seki, K. Takahashi, K. Miyokawa, K. Handa, H. Katsuta, S. Yamaguchi, K. Yoshimoto, E. Itagaki, S. Nagamatsu, H. Ishida
  • Journal Title: J Kyorin Med Soc 39 Pages: 31-36
• [Journal Article] Visceral fat thickness in overweight men correlates with alterations in serum fatty acid composition. (2008)
  • Author(s): T. Kishino, K. Watanabe, T. Urata, M. Takano, T. Uemura, K. Nishikawa, Y. Mine, M. Matsumoto, K. Ohtsuka, H. Ohnishi, H. Mori, S. Takahashi, H. Ishida, T. Watanabe
  • Journal Title: Clin Chim Acta 398 Pages: 57-62
• [Journal Article] Increased bone resorption may play a crucial role in the occurrence of osteopenia in patients with type 2 diabetes: possible involvement of accelerated polyol pathway in its pathogenesis. (2008)
  • Author(s): M. Takizawa, K. Suzuki, T. Matsubayashi, M. Kikuyama, H. Suzuki, K. Takahashi, H. Katsuta, J. Mitsuhashi, S. Nishida, S. Yamaguchi, K. Yoshimoto, E. Itagaki, H. Ishida
  • Journal Title: Diabetes Res Clin Pract 82 Pages: 119-126
• [Journal Article] JNK-and IκB-dependent pathways regulate MCP-1, but not adiponectin, release from artificially hypertrophied 3T3-L1 adipocytes preloaded with palmitate in vitro. (2008)
  • Author(s): K. Takahashi, S. Yamaguchi, T. Shimoyama, H. Seki, K. Miyokawa, H. Katsuta, T. Tanaka, K. Yoshimoto, H. Ohno, S. Nagamatsu, H. Ishida
  • Journal Title: Am J Physiol 294
• [Journal Article] JNK- and IkB-dependent pathways regulate MCP-1, but not adiponectin, release from artificially hypertrophied 3T3-L1 adipocytes preloaded with palmitate in vitro. (2008)
  • Author(s): T. Takahashi, H. Ishida, et al.
  • Journal Title: Am J Physiol 294
  • Peer Reviewed
• [Journal Article] JNK-and IκB-dependent pathways regulate MCP-1,but not adiponectin,release from artificially hypertrophied 3T3-L1 adipocytes preloaded with palmitate in vitro. (2008)
  • Author(s): K.Takahashi, H.Ishida, et. al.
  • Journal Title: Am J Physiol 294(in press)
  • Peer Reviewed
• [Journal Article] SHP-2 positively regulates adipogenic differentiation in 3T3-L1 cells. (2007)
  • Author(s): T.Uehara, H.Ishida, et. al.
  • Journal Title: Int J Mol Med 19 Pages: 895-900
  • Peer Reviewed
• [Journal Article] Gliclazide inhibits proliferation but stimulates differentiation of white and brown adipocytes. (2007)
  • Author(s): N.Nakano, H.Ishida, et. al.
  • Journal Title: J Biochem 142 Pages: 639-645
  • NAID: 10020095721
  • Peer Reviewed
• [Presentation] Hypoxia- independent VEGF120 secretion is stimulated by increase of endogenous oxidative stress through PI3K-dependent pathways in artificially hypertrophied 3T3-L1 adipocytes: The regulation by distinct mechanism from MCP-1 via JNK and p38 MAPK pathways (2010)
  • Author(s): K. Takahashi, S. Yamaguchi, T. Shimoyama, T. Tanaka, K. Miyokawa, K. Handa, H. Katsuta, S. Nishida, K. Yoshimoto, H. Ishida
  • Organizer: 14th International Congress of Endocrinology
  • Place of Presentation: Kyoto
• [Presentation] 肥大化脂肪細胞におけるVEGF120分泌の制御機構について-MCP-1分泌機構との相違- (2009)
  • Author(s): 高橋和人, 山口真哉, 下山達宏, 田中利明, 三代川可織, 半田桂子, 勝田秀紀, 西田進, 吉元勝彦, 永松信哉, 石田均
  • Organizer: 第52回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
• [Presentation] Glucolipotoxicityによる膵β細胞からのMCP-1分泌の増加と細胞内情報伝達系の関与 (2008)
  • Author(s): 関博之, 高橋和人, 三代川可織, 半田桂子, 勝田秀紀, 下山達宏, 田中利明, 山口真哉, 吉元勝彦, 板垣英二, 永松信哉, 石田均
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
• [Presentation] Glucolipotoxicityによる膵β細胞からのMCP-1分泌の増加と細胞内情報伝達系の関与. (2008)
  • Author(s): 関 博之, 石田 均ら
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
• [Presentation] 膵β細胞からのMCP-1分泌に及ぼす高濃度グルコースおよび脂肪酸の影響について (2007)
  • Author(s): 関博之, 高橋和人, 伊藤英介, 勝田秀紀, 田中利明, 下山達宏, 山口真哉, 吉元勝彦, 永松信哉, 石田均
  • Organizer: 第50回日本糖尿病学会年次学術集会
  • Place of Presentation: 仙台
• [Presentation] 膵β細胞からのMCP-1分泌に及ぼす高濃度グルコースおよび脂肪酸の影響について. (2007)
  • Author(s): 関 博之, 石田 均, ら
  • Organizer: 第50回日本糖尿病学会年次学術集会
  • Place of Presentation: 仙台
• [Book] 膵臓移植. 出月康夫、野澤眞澄監修 (2009)
  • Author(s): 西田 進, 石田 均ら(分担執筆)
  • Total Pages: 474
  • Publisher: シュプリンガー・ジャパン