Effects of diabetes-related lipid dysregulation in astrocytes on cognitive functions

• Project/Area Number: 16K09776
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Tokyo Medical University (2018); The University of Tokyo (2016-2017)
• Principal Investigator: Suzuki Ryo 東京医科大学, 医学部, 准教授 (20396732)
• Research Collaborator: Chou Shengpu ; Watanabe Ryusuke ; Terai Ai ; Kamei Nozomu ; Kadowaki Takashi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 糖尿病 / 脳脂質代謝 / コレステロール合成 / SCAP / AMPK / 内科 / 脳・神経 / 脂質 / 細胞・組織

Outline of Final Research Achievements

Brain from a subject with diabetes mellitus exhibits elevated activity of AMPK and reduction of SCAP. AMPK signaling potentially promotes transport of SCAP-SREBP complex from ER to Golgi via Rab2 pathway. Reduction of SCAP in astrocytes can inhibit growth and maturation of adjacent neurons.

Academic Significance and Societal Importance of the Research Achievements

糖尿病が認知機能を低下させるメカニズムは未だ不明な点が多い。アストロサイトにおけるエネルギー状態と脂質代謝の変化によってニューロンの成熟状態が影響を受ける新規分子経路を提唱する結果である。

Research Products

• [Journal Article] Effect of short-term treatment with sitagliptin or glibenclamide on daily glucose fluctuation in drug-naive Japanese patients with type 2 diabetes mellitus (2018)
  • Author(s): Suzuki Ryo、Eiki Jun-ichi、Moritoyo Takashi、Furihata Kenichi、Wakana Akira、Ohta Yukari、Tokita Shigeru、Kadowaki Takashi
  • Journal Title: Diabetes, Obesity and Metabolism Volume: 20 Issue: 9 Pages: 2274-2281
  • DOI: 10.1111/dom.13364
  • Peer Reviewed
• [Journal Article] Membrane-Initiated Estrogen Receptor Signaling Mediates Metabolic Homeostasis via Central Activation of Protein Phosphatase 2A (2018)
  • Author(s): Ueda Kazutaka、Takimoto Eiki、Lu Qing、Liu Pangyen、Fukuma Nobuaki、Adachi Yusuke、Suzuki Ryo、Chou Shengpu、Baur Wendy、Aronovitz Mark J.、Greenberg Andrew S.、Komuro Issei、Karas Richard H.
  • Journal Title: Diabetes Volume: 67 Issue: 8 Pages: 1524-1537
  • DOI: 10.2337/db17-1342
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The RNA Methyltransferase Complex of WTAP, METTL3, and METTL14 Regulates Mitotic Clonal Expansion in Adipogenesis. (2018)
  • Author(s): Kobayashi M, Ohsugi M, Sasako T, Awazawa M, Umehara T, Iwane A, Kobayashi N, Okazaki Y, Kubota N, Suzuki R, Waki H, Horiuchi K, Hamakubo T, Kodama T, Aoe S, Tobe K, Kadowaki T, Ueki K
  • Journal Title: Mol. Cell Biol. Volume: 38 Issue: 16 Pages: 81-91
  • DOI: 10.1128/mcb.00116-18
  • Peer Reviewed / Open Access
• [Journal Article] Gastrointestinal symptom prevalence depends on disease duration and gastrointestinal region in type 2 diabetes mellitus (2017)
  • Author(s): Fujishiro M, Kushiyama A, Yamazaki H, Kaneko S, Koketsu Y, Yamamotoya T, Kikuchi T, Sakoda H, Suzuki R, Kadowaki T
  • Journal Title: World J Gastroenterol Volume: 23 Issue: 36 Pages: 6694
  • DOI: 10.3748/wjg.v23.i36.6694
  • URL: https://localhost/en/publications/b59c66b8-7150-4729-93a4-df6431c513be
  • Peer Reviewed / Open Access
• [Journal Article] Development of an Automatic Puncturing and Sampling System for a Self-Monitoring Blood Glucose Device (2017)
  • Author(s): Abe-Doi M, Oe M, Murayama R, Takahashi M, Zushi Y, Tanabe H, Takamoto I, Suzuki R, Yamauchi T, Kadowaki T, Komiyama C, Sanada H
  • Journal Title: Diabetes Technol Ther Volume: 19 Issue: 11 Pages: 651-659
  • DOI: 10.1089/dia.2017.0163
  • Peer Reviewed
• [Journal Article] Willingness of patients with diabetes to use an ICT-based self-management tool: a cross-sectional study (2017)
  • Author(s): Shibuta T, Waki K, Tomizawa N, Igarashi A, Yamamoto-Mitani N, Yamaguchi S, Fujita H, Kimura S, Fujiu K, Waki H, Izumida Y, Sasako T, Kobayashi M, Suzuki R, Yamauchi T, Kadowaki T, Ohe K.
  • Journal Title: BMJ Open Diabetes Res Care Volume: 5 Issue: 1 Pages: e000322-e000322
  • DOI: 10.1136/bmjdrc-2016-000322
  • Peer Reviewed / Open Access
• [Journal Article] Psychological and behavioural patterns of stigma among patients with type 2 diabetes: A cross-sectional study (2017)
  • Author(s): Kato A, Fujimaki Y, Fujimori S, Isogawa A, Onishi Y, Suzuki R, Yamauchi T, Ueki K, Kadowaki T, Hashimoto H.
  • Journal Title: BMJ Open Volume: 7 Issue: 3 Pages: e013425-e013425
  • DOI: 10.1136/bmjopen-2016-013425
  • URL: https://pure.teikyo.jp/en/publications/6194803f-f097-432e-ae18-27754ff68112
  • Peer Reviewed / Open Access
• [Journal Article] Association between self-stigma and self-care behaviors in patients with type 2 diabetes: a cross-sectional study. (2016)
  • Author(s): Kato A, Fujimaki Y, Fujimori S, Isogawa A, Onishi Y, Suzuki R, Yamauchi T, Ueki K, Kadowaki T, Hashimoto H
  • Journal Title: BMJ Open Diabetes Res Care Volume: 4 Issue: 1 Pages: e000156-e000156
  • DOI: 10.1136/bmjdrc-2015-000156
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A case of insulin allergy successfully managed using multihexamer-forming insulin degludec combined with liraglutide (2016)
  • Author(s): Fujishiro M, Izumida Y, Takemiya S, Kuwano Y, Takamoto I, Suzuki R, Yamauchi T, Ueki K, Kadowaki T.
  • Journal Title: Diabet Med Volume: 33 Issue: 11
  • DOI: 10.1111/dme.12998
  • Peer Reviewed
• [Journal Article] A qualitative study on the impact of internalized stigma on type 2 diabetes self-management (2016)
  • Author(s): Kato A, Fujimaki Y, Fujimori S, Izumida Y, Suzuki R, Ueki K, Kadowaki T, Hashimoto H
  • Journal Title: Patient Education and Counselinｇ Volume: in press Issue: 7 Pages: 1233-1239
  • DOI: 10.1016/j.pec.2016.02.002
  • Peer Reviewed
• [Journal Article] Shear stress-normal stress (Pressure) Ratio (SPR) decides forming callus in patients with diabetic neuropathy (2016)
  • Author(s): Amemiya A, Noguchi H, Oe M, Takehara K, Ohashi Y, Suzuki R, Yamauchi T, Kadowaki T, Sanada H, Mori T.
  • Journal Title: Journal of Diabetes Research Volume: - Pages: 3157123-3157123
  • DOI: 10.1155/2016/3157123
  • Peer Reviewed / Open Access
• [Presentation] 認知症と糖尿病 (2019)
  • Author(s): 鈴木亮
  • Organizer: 第34回日本静脈経腸栄養学会学術集会
  • Invited
• [Presentation] 高齢者糖尿病と認知症（血糖コントロール目標も含めて） (2018)
  • Author(s): 鈴木亮
  • Organizer: 第33回日本糖尿病合併症学会・第24回日本糖尿病眼学会総会
  • Invited
• [Presentation] 高齢者における糖尿病の管理 (2018)
  • Author(s): 鈴木亮
  • Organizer: 日本成人病（生活習慣病）学会 第9回教育集会
  • Invited
• [Presentation] 糖尿病と認知症 (2018)
  • Author(s): 鈴木 亮
  • Organizer: 第55回 日本糖尿病学会関東甲信越地方会
  • Invited
• [Presentation] 脳グリア細胞においてステロールセンサー分子SCAPはユビキチンプロテアソーム経路を介して量制御される (2017)
  • Author(s): 渡辺隆介、鈴木 亮、亀井 望、周聖浦、寺井 愛、門脇 孝
  • Organizer: 第60回 日本糖尿病学会年次学術集会
• [Presentation] アストロサイトにおけるステロールセンサー分子SCAPの欠損誘導は認知機能障害と行動変化を引き起こす (2017)
  • Author(s): 周聖浦、鈴木 亮、渡辺隆介、寺井 愛、亀井 望、門脇 孝
  • Organizer: 第60回 日本糖尿病学会年次学術集会
• [Presentation] 糖尿病における認知障害・認知症 (2017)
  • Author(s): 鈴木 亮
  • Organizer: 第59回 日本老年医学会学術集会
  • Invited
• [Presentation] 脳内インスリンの役割とその作用不全 (2017)
  • Author(s): 鈴木 亮
  • Organizer: 第32回 日本糖尿病合併症学会
  • Invited
• [Presentation] ステロールセンサー分子SCAPのアストロサイトにおける欠損誘導は記憶障害と行動変化を引き起こす (2016)
  • Author(s): 周聖浦、鈴木亮、渡辺隆介、寺井愛、亀井望、門脇孝
  • Organizer: 第59回日本糖尿病学会年次学術集会
  • Place of Presentation: 京都
• [Presentation] 脳グリア細胞においてステロールセンサー分子SCAPはユビキチン-プロテアソーム経路を介して量制御される (2016)
  • Author(s): 渡辺隆介、鈴木亮、亀井望、周聖浦、寺井愛、門脇孝
  • Organizer: 第59回日本糖尿病学会年次学術集会
  • Place of Presentation: 京都
• [Presentation] 脳内コレステロール代謝と認知機能 (2016)
  • Author(s): 鈴木亮
  • Organizer: 第16回日本抗加齢医学会総会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] 脳のインスリン作用不全に伴う脂質合成異常と糖尿病関連病態の形成 (2016)
  • Author(s): 鈴木亮
  • Organizer: 第31回日本糖尿病合併症学会
  • Place of Presentation: 仙台
  • Invited