The metabolic effect and pathophysiological role of skeletal muscle AMPK in streptozocin-induced diabetic mice

• Project/Area Number: 16K19549
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Department of Clinical Research, National Hospital Organization Kyoto Medical Center (2017); National Institute for Physiological Sciences (2016)
• Principal Investigator: Yokota Shigefumi 独立行政法人国立病院機構(京都医療センター臨床研究センター), 内分泌代謝高血圧研究部, 研究員 (50725281)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: AMPK / streptozotocin / 臓器連関 / myokine / IL-6 / myonectin / leptin / インスリン依存性糖尿病 / マイオカイン / レプチン / 臓器関連間

Outline of Final Research Achievements

AMP kinase (AMPK) is a metabolic sensor that plays an important role in obesity and diabetes. It was observed that found that streptozotocin (STZ)-induced diabetic mice activated AMPK in skeletal muscle. Skeletal muscle-specific dominant negative AMPK-expressing transgenic mice (DN-AMPK Tg mice) suppressed metabolic abnormalities in STZ-induced insulin-deficient diabetes. The study revealed that IL-6, myonectin, leptin and etc affect metabolic abnormalities of STZ-induced diabetes.

Research Products

• [Journal Article] Activation of AMPK-Regulated CRH Neurons in the PVH is Sufficient and Necessary to Induce Dietary Preference for Carbohydrate over Fat. (2018)
  • Author(s): Okamoto S, Sato T, Tateyama M, Kageyama H, Maejima Y, Nakata M, Hirako S, Matsuo T, Kyaw S, Shiuchi T, Toda C, Sedbazar U, Saito K, Asgar NF, Zhang B, Yokota S, Kobayashi K, Foufelle F, Ferré P, Nakazato M, Masuzaki H, Shioda S, Yada T, Kahn BB, Minokoshi Y.
  • Journal Title: Cell Rep. Volume: 22 Issue: 3 Pages: 706-721
  • DOI: 10.1016/j.celrep.2017.11.102
  • NAID: 120007001417
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Activation of SF1 Neurons in the Ventromedial Hypothalamus by DREADD Technology Increases Insulin Sensitivity in Peripheral Tissues. (2017)
  • Author(s): Coutinho EA, Okamoto S, Ishikawa AW, Yokota S, Wada N, Hirabayashi T, Saito K, Sato T, Takagi K, Wang CC, Kobayashi K, Ogawa Y, Shioda S, Yoshimura Y, Minokoshi Y
  • Journal Title: Diabetes Volume: 66 Issue: 9 Pages: 2372-2372
  • DOI: 10.2337/db16-1344
  • Peer Reviewed / Open Access
• [Presentation] 肥満症患者の糖代謝機能・骨格筋量制御における筋肉由来液性因子・myostatinの病態意義 (2018)
  • Author(s): 横田繁史,増田慎也、田中将志、山陰一、村中和哉、井上隆之、北野隆司、真田樹義、石井好二郎、日下部徹、島津章、浅原哲子
  • Organizer: 第38回日本肥満学会
• [Presentation] Role of myokines in metabolic abnormalities of streptozotocin-induced diabetes. (2017)
  • Author(s): 横田繁史, 箕越靖彦
  • Organizer: 第91回日本生理学会
  • Place of Presentation: 静岡県浜松市 アクトシティホール
  • Year and Date: 2017-03-27
• [Presentation] Role of myokines in metabolic abnormalities of streptozotocin-induced diabetes. (2016)
  • Author(s): 横田繁史, 箕越靖彦
  • Organizer: 第37回日本肥満学会
  • Place of Presentation: 東京都千代田区 東京ファッションタウン
  • Year and Date: 2016-10-07