For clinical application of glucokinase activator

• Project/Area Number: 23791040
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Yokohama City University
• Principal Investigator: NAKAMURA Akinobu 横浜市立大学, 附属病院, 助教 (70552420)
• 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: グルコキナーゼ / 膵β細胞量

Research Abstract

We investigated the mechanisms by which glucokinase activator (GKA) stimulates beta cell function and proliferation and we then explored therapeutic strategy by which GKA worked more effectively. GKA-stimulated Irs2 expression affected beta cell proliferation, but not beta cell function. Oxidative stress could diminish the effects of GKA on the changes in expression of genes involved in beta cell function and proliferation. A combination of GKA and an incretin-related agent might be effective.

Research Products

• [Journal Article] Factors associated with the glucose-lowering effect of vildagliptin identified from the results of the oral glucose tolerance test in Japanese patients with type 2 diabetes (2013)
  • Author(s): Nakamura A
  • Journal Title: Endocrine Journal Volume: 60 Pages: 45-49
  • NAID: 10031156721
  • Peer Reviewed
• [Journal Article] Control of beta cell function and proliferation in mice stimulated by small-molecule glucokinase activator under various conditions (2012)
  • Author(s): Nakamura A, Togashi Y, Orime K, Sato K, Shirakawa J, Ohsugi M, Kubota N, Kadowaki T, Terauchi Y
  • Journal Title: Diabetologia Volume: (In press) Issue: 6 Pages: 1745-1754
  • DOI: 10.1007/s00125-012-2521-5
  • Peer Reviewed
• [Journal Article] Protection from nonalcoholic steatohepatitis and liver tumorigenesis in high fat-fed insulin receptor substrate-1-knockout mice despite insulin resistance. (2012)
  • Author(s): Nakamura A, Tajima K, Zolzaya K, Sato K, Inoue R, Yoneda M, Fujita K, Nozaki Y, Kubota KC, Haga H, Kubota N, Nagashima Y, Nakajima A, Maeda S, Kadowaki T, Terauchi Y
  • Journal Title: Diabetologia Volume: 55(12) Issue: 12 Pages: 3382-3391
  • DOI: 10.1007/s00125-012-2703-1
  • Peer Reviewed
• [Journal Article] Impact of the dipeptidyl peptidase-4 inhibitor vildagliptin on glucose tolerance, beta cell function and mass in insulin receptor substrate-2-knockout mice fed a high-fat diet (2012)
  • Author(s): Sato K, Nakamura A, Shirakawa J, Muraoka T, Togashi Y, Shinoda K, Orime K, Kubota N, Kadowaki T, Terauchi Y
  • Journal Title: Endocrinology Volume: 153(3) Issue: 3 Pages: 1093-102
  • DOI: 10.1210/en.2011-1712
  • Peer Reviewed
• [Journal Article] 糖尿病の薬物療法‐最新の治療と将来展望 (2012)
  • Author(s): 中村昭伸、寺内康夫
  • Journal Title: グルコキナーゼ活性化薬 カレントテラピー Volume: 30 Pages: 85-90
• [Journal Article] Effect of long-term treatment with a small molecule glucokinase activator on glucose metabolism, lipid profiles, and hepatic function (2011)
  • Author(s): Nakamura A, Shimazaki H, Ohyama S, Eiki J, Terauchi Y
  • Journal Title: J Diabetes Invest Volume: 2 Issue: 4 Pages: 276-279
  • DOI: 10.1111/j.2040-1124.2011.00104.x
  • Peer Reviewed
• [Journal Article] 膵β細胞の分化、増殖制御と糖尿病治療 糖代謝を介した膵β 細胞増殖促進薬 (2011)
  • Author(s): 中村昭伸、寺内康夫
  • Journal Title: 細胞 Volume: 43 Pages: 469-472
• [Journal Article] 次世代の 2 型糖尿病薬物治療 開発中の次世代の治療薬 GK活性化薬、GPR119 受容体アゴニスト (2011)
  • Author(s): 中村昭伸、寺内康夫
  • Journal Title: 月刊Mebio Volume: 28 Pages: 104-110
• [Journal Article] 糖尿病治療最前線2011 新しい糖尿病治療薬 9 グルコキナーゼ活性化薬の現状と展望 (2011)
  • Author(s): 中村昭伸、寺内康夫
  • Journal Title: 月刊糖尿病 Volume: 3 Pages: 114-123
• [Journal Article] 次世代の2型糖尿病薬物治療 開発中の次世代の治療薬 GK活性化薬、GPR119受容体アゴニスト (2011)
  • Author(s): 中村昭伸、寺内康夫
  • Journal Title: Mebio Volume: 28 Pages: 104-110
• [Journal Article] 糖尿病治療最前線2011 新しい糖尿病治療薬9：グルコキナーゼ活性化薬の現状と展望 (2011)
  • Author(s): 中村昭伸、寺内康夫
  • Journal Title: 月刊糖尿病 Volume: 3 Pages: 114-123
• [Journal Article] 膵β細胞の分化、増殖制御と糖尿病治療 糖代謝を介した膵β細胞増殖促進薬 (2011)
  • Author(s): 中村昭伸、寺内康夫
  • Journal Title: 細胞 Volume: 43 Pages: 469-472
• [Presentation] Beta Cell Function and Proliferation in Response to Small Molecule Glucokinase Activator under Various Conditions (2011)
  • Author(s): Akinobu Nakamura
  • Organizer: 71th Scientific Sessions for American Diabetes Association
  • Place of Presentation: San Diego, California, USA
• [Presentation] 膵β細胞の再生を目指して The role of IRS-2 in the regulation of pancreatic beta cell mass in response to small molecule glucokinase activator (2011)
  • Author(s): 中村昭伸
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: ロイトン札幌(北海道)(招待講演)
• [Presentation] グルコキナーゼ活性化薬が膵β細胞機能・増殖に与える影響 (2011)
  • Author(s): 中村昭伸
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌プリンスホテル(北海道)
• [Presentation] Beta Cell Function and Proliferation in Response to Small Molecule Glucokinase Activator under Various Conditions (2011)
  • Author(s): Nakamura A, Togashi Y, Orime K, Sato K, Shirakawa J, Terauchi Y
  • Organizer: 71th Scientific Sessions for American Diabetes Association
  • Place of Presentation: San Diego, California
• [Presentation] グルコキナーゼ活性化薬が膵β細胞機能・増殖に与える影響 (2011)
  • Author(s): 中村昭伸、富樫優、折目和基、佐藤光一郎、白川純、田波律子、伊藤譲、寺内康夫
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌プリンスホテル（札幌市）
• [Presentation] 膵β細胞の再生を目指して The role of IRS-2 in the regulation of pancreatic beta cell mass in response to small molecule glucokinase activator (2011)
  • Author(s): 中村昭伸、寺内康夫
  • Organizer: 第54回日本糖尿病学会年次学術集会シンポジウム(招待講演)
  • Place of Presentation: ロイトン札幌（札幌市）
• [Book] カレントテラピー (2012)
  • Author(s): 中村昭伸
  • Total Pages: 6
  • Publisher: 糖尿病の薬物療法‐最新の治療と将来展望 グルコキナーゼ活性化薬