Comprehensive analysis of autophagy in the pathogenesis of diabetes and its complications

• Project/Area Number: 26293217
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Maegawa Hiroshi 滋賀医科大学, 医学部, 教授 (00209363)
• Co-Investigator(Renkei-kenkyūsha): KUME Shinji 滋賀医科大学, 内科, 講師 (00452235) ; MAEDA Shiro 琉球大学, 医学(系)研究科, 教授 (50314159)
• Research Collaborator: YAMAHARA Mako ; TAGAWA Atsuko ; YOSHIBAYASHI Mamoru
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000); Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2015: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: 糖尿病 / 肥満 / 糖尿病性腎症 / 腎臓 / オートファジー / 内科 / 脳・神経 / 飢餓 / ケトン体 / ケトン産生

Outline of Final Research Achievements

Autophagy is an intracellular catabolic process that can maintain cellular homeostasis during several stress conditions such as starvation and mitochondrial oxidative stress. Growing evidences have shown that altered autophagy activity is associated with the pathogenesis of a variety of diseases. The present study revealed that mammalian autophagy is essential for maintaining energy homeostasis via enhancing ketogenesis during starvation, and that diabetes-related dysregulation of autophagy is involved in the pathogenesis of diabetic vascular complications, such as diabetic nephropathy. These observation suggest that autophagy activation should shed a light on therapy for diabetic complications and contribute to health promotion in diabetic patients.

Research Products

• [Int'l Joint Research] Baylor College of Medicine(米国)
• [Journal Article] 糖尿病性腎症の発症進展におけるオートファジーの関与 (2017)
  • Author(s): 山原 康佑, 山原 真子, 久米 真司
  • Journal Title: 日本腎臓学会誌 Volume: 59 Pages: 50-57
• [Journal Article] オートファジーと糖尿病性腎症、糸球体上皮細胞障害 (2017)
  • Author(s): 山原 真子, 山原 康佑, 久米 真司
  • Journal Title: 臨床病理 Volume: 65 Pages: 667-673
• [Journal Article] ポドサイトにおけるオートファジーの役割 (2017)
  • Author(s): 吉林 護, 久米 真司
  • Journal Title: 医学のあゆみ Volume: 263 Pages: 159-163
• [Journal Article] 糖尿病性腎症におけるオートファジーの役割 (2017)
  • Author(s): 久米 真司
  • Journal Title: BIO Clinica Volume: 32 Pages: 448-453
• [Journal Article] Emerging role of mammalian autophagy in ketogenesis to overcome starvation. (2016)
  • Author(s): Takagi A, Kume S, Maegawa H, Uzu T.
  • Journal Title: Autophagy. 2016;12(4):709-10. Volume: 12 Issue: 4 Pages: 709-10
  • DOI: 10.1080/15548627.2016.1151597
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mammalian autophagy is essential for hepatic and renal ketogenesis during starvation. (2016)
  • Author(s): Takagi A, Kume S, Kondo M, Nakazawa J, Chin-Kanasaki M, Araki H, Araki S, Koya D, Haneda M, Chano T, Matsusaka T, Nagao K, Adachi Y, Chan L, Maegawa H, Uzu T.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 18944-18944
  • DOI: 10.1038/srep18944
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impaired podocyte autophagy exacerbates proteinuria in diabetic nephropathy. (2016)
  • Author(s): Tagawa A, Yasuda M, Kume S, Ymahara K, Nakazawa J, Chin-Kanasaki M, Araki H, Araki SI, Koya D, Asanuma K, Kim EH, Haneda M, Kajiwara N, Hayashi K, Ohashi H, Ugi S, Maegawa H, Uzu T
  • Journal Title: Diabetes. Volume: - Issue: 3 Pages: 755-767
  • DOI: 10.2337/db15-0473
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Emerging role of podocyte autophagy in the progression of diabetic nephropathy. (2015)
  • Author(s): Yasuda-Yamahara M, Kume S, Tagawa A, Maegawa H, Uzu T.
  • Journal Title: Autophagy Volume: 11 Issue: 12 Pages: 2385-2386
  • DOI: 10.1080/15548627.2015.1115173
  • Peer Reviewed / Open Access
• [Journal Article] Lamp-2 deficiency prevents high-fat diet-induced obese diabetes via enhancing energy expenditure. (2015)
  • Author(s): Yasuda-Yamahara M, Kume S, Yamahara K, Nakazawa J, Chin-Kanasaki M, Araki H, Araki S, Koya D, Haneda M, Ugi S, Maegawa H, Uzu T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 18 Issue: 2 Pages: 249-255
  • DOI: 10.1016/j.bbrc.2015.08.010
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 肥満と腎臓病 新規治療標的の開発を目指して (2014)
  • Author(s): 久米真司 前川聡
  • Journal Title: 肥満研究 Volume: 20 Pages: 160-167
  • NAID: 40020321227
  • Acknowledgement Compliant
• [Presentation] 糖尿病性腎症進展における糸球体血管内皮障害とポドサイトオートファジーの関連 (2018)
  • Author(s): 吉林護、久米真司、武田尚子、大澤紀之、金崎雅美、中江由希、横井秀基、向山政志、荒木信一、前川聡
  • Organizer: 第61回日本糖尿病学会年次学術集会
• [Presentation] Effect of interaction between podocyte autophagy and glomerular endothelial dysfunction on progression of diabetic nephropathy (2018)
  • Author(s): Yoshibayashi M, Kume S, Takeda N, Osawa N, Chin-Kanasaki M, Nakae Y, Yokoi H, Mukoyama M, Araki S-i, Maegawa H
  • Organizer: The ISN Frontiers meeting 2018
• [Presentation] 糖尿病性腎症のポドサイト障害における糸球体血管内皮障害とポドサイトオートファジーの役割 (2017)
  • Author(s): 吉林 護, 久米 真司, 武田 尚子, 大澤 紀之, 金崎 雅美, 中江 由紀, 横井 秀基, 向山 政志, 荒木 信一, 前川 聡
  • Organizer: 第32回日本糖尿病合併症学会
• [Presentation] 糖尿病に伴うポドサイト障害における食餌中アミノ酸バランスの重要性 (2017)
  • Author(s): 吉田 尚平, 久米 真司, 武田 尚子, 大澤 紀之, 金崎 雅美, 古家 大祐, 安達 祐介, 荒木 信一, 前川 聡
  • Organizer: 第32回日本糖尿病合併症学会
• [Presentation] New therapeutic targets of diabetic nephropathy: lessons learned from calorie restriction (2017)
  • Author(s): Shinji Kume
  • Organizer: The 60th Annual Meeting of the Japanese Society of Nephrology
  • Int'l Joint Research / Invited
• [Presentation] Role of autophagy in diabetic nephropathy and renal ketogenesis (2016)
  • Author(s): Kume S, Maegawa H
  • Organizer: Kidney Week 2016
  • Place of Presentation: Chicago, USA
  • Year and Date: 2016-11-16
  • Int'l Joint Research / Invited
• [Presentation] 糸球体上皮細胞におけるオートファジー不全は糖尿病性腎症における蛋白尿を増悪させる. (2015)
  • Author(s): 田川 安都子, 安田 真子, 久米 真司, 中澤 純, 金崎 雅美, 荒木 久澄,荒木 信一, 古家 大祐, 羽田 勝計, 宇津 貴, 前川 聡.
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 2015-06-05
• [Presentation] 餓時の糖新生ならびにケトン産生における肝腎オートファジーの役割. (2015)
  • Author(s): 高木 彩乃, 久米 真司, 中澤 純, 金崎 雅美, 荒木 久澄, 荒木 信一, 宇津 貴, 前川 聡.
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 2015-06-05
• [Presentation] シャペロン介在性オートファジー欠損は高脂肪食負荷肥満糖尿病の発症を抑制する. (2015)
  • Author(s): 安田 真子, 久米 真司, 中澤 純, 金崎 雅美, 荒木 久澄, 荒木 信一, Paul Saftig, 宇津 貴, 前川 聡.
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: 山口県下関市
  • Year and Date: 2015-05-21
• [Presentation] Podocyte Autophagy is Associated with the Progression of Proteinuria in Diabetic Nephropathy (2014)
  • Author(s): Mako Yasuda, Atsuko Tagawa, Shinji Kume, Yuki Tanaka, Kosuke Yamahara, Hisazumi Araki, Keiji Isshiki, Shin-ichi Araki, Daisuke Koya, Masakazu Haneda, Takashi Uzu, Hiroshi Maegawa
  • Organizer: American Diabetes Association (ADA) 74th Scientific Sessions
  • Place of Presentation: サンフランシスコ, アメリカ合衆国
  • Year and Date: 2014-06-13 – 2014-06-17
• [Presentation] The Role of Starvation-induced Autophagy in Gluconeogenesis and Ketogenesis (2014)
  • Author(s): Ayano Takagi, Shinji Kume, Yuki Tanaka, Hisazumi Araki, Keiji Isshiki, Shin-Ichi Araki, Takashi Uzu, Hiroshi Maegawa
  • Organizer: American Diabetes Association (ADA) 74th Scientific Sessions
  • Place of Presentation: サンフランシスコ, アメリカ合衆国
  • Year and Date: 2014-06-13 – 2014-06-17
• [Presentation] 飢餓時の糖新生ならびにケトン産生におけるオートファジーの役割 (2014)
  • Author(s): 高木 彩乃, 久米 真司, 金崎 雅美, 荒木 久澄, 一色 啓二, 荒木 信一, 茶野 徳宏, 柏木 厚典, 宇津 貴, 前川 聡
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] 糸球体上皮細胞オートファジー不全は糖尿病性腎症における蛋白尿を増悪させる (2014)
  • Author(s): 安田 真子, 田川 安都子, 久米 真司, 田中 敬, 金崎 雅美, 荒木 久澄, 一色 啓二, 荒木 信一, 古家 大祐, 羽田 勝計, 柏木 厚典, 宇津 貴, 前川 聡
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] Insufficient podocyte autophagy is associated with the progression of proteinuria in diabetic nephropathy. (2014)
  • Author(s): Mako Yasuda, Atsuko Tagawa, Shinji Kume, Yuki Tanaka, Shin-ichi Araki, Daisuke Koya, Masakazu Haneda, Takashi Uzu, Hiroshi Maegawa
  • Organizer: The 14th Asian Pacific Congress of Nephrology (APCN2014)
  • Place of Presentation: 東京
  • Year and Date: 2014-05-14 – 2014-05-17