The prevention and treatment of obesity and diabetes with BDNF, a myokine derived from skeletal muscle

• Project/Area Number: 26350885
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Niigata University
• Principal Investigator: HANYU Osamu 新潟大学, 医歯学総合病院, 講師 (10452054)
• Co-Investigator(Kenkyū-buntansha): 曽根 博仁 新潟大学, 医歯学系, 教授 (30312846)
• Co-Investigator(Renkei-kenkyūsha): NAWA Hiroyuki 新潟大学, 脳研究所, 教授 (50183083)
• Research Collaborator: FURUKAWA Kazuo
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: BDNF / 糖尿病 / 肥満 / 脳由来神経栄養因子 / 運動療法 / マイオカイン / 生活習慣病

Outline of Final Research Achievements

Brain-derived neurotrophic factor (BDNF) is a possible anti-obesity and anti-diabetes agent with its anorectic and hypoglycemic effect. Recently BDNF is considered as one of myokines which is produced in skeletal muscle. We demonstrated that BDNF reduces blood glucose level via suppression of glucagon secretion from pancreas. In addition, advanced glycation end products (AGEs) induces BDNF release from human platelets through the activation of the Src family kinase pathway (Furukawa, K. et al. Cardiovasc Diabetol. 2017;16(1):20). Considering the toxic action of AGEs and the protective roles of BDNF, it can be hypothesized that AGE-induced BDNF release is a biological defense system in the early phase of diabetes. Chronic elevation of AGEs may induce depletion or downregulation of BDNF in platelets during the progression of diabetes mellitus.

Research Products

• [Journal Article] Advanced glycation end products induce brain-derived neurotrophic factor release from human platelets through the Src-family kinase activation (2017)
  • Author(s): Furukawa, K. Fuse, I. Iwakura, Y. Sotoyama, H. Hanyu, O. Nawa, H. Sone, H. Takei, N.
  • Journal Title: Cardiovascular diabetology Volume: 16 Issue: 1 Pages: 20-20
  • DOI: 10.1186/s12933-017-0505-y
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Unstable body weight and incident type 2 diabetes mellitus - A meta-analysis (in press) (2017)
  • Author(s): Kodama S, Fujihara K, Ishiguro H, Horikawa C, Ohara N, Yachi Y, Tanaka S, Shimano H, Kato K, Hanyu O, Sone H
  • Journal Title: Journal of diabetes investigation Volume: - Issue: 4 Pages: 501-509
  • DOI: 10.1111/jdi.12623
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Is the Proportion of Carbohydrate Intake Associated with the Incidence of Diabetes Complications?-An Analysis of the Japan Diabetes Complications Study. (2017)
  • Author(s): Horikawa C, Yoshimura Y, Kamada C, Tanaka S, Tanaka S, Matsunaga S, Hanyu O, Araki A, Ito H, Tanaka A, Ohashi Y, Akanuma Y, Sone H.
  • Journal Title: Nutrients Volume: - Issue: 2 Pages: 113-113
  • DOI: 10.3390/nu9020113
  • NAID: 120005997765
  • Peer Reviewed / Open Access
• [Journal Article] Quantitative assessment of genetic testing for type 2 diabetes mellitus based on findings of genome-wide association studies (2016)
  • Author(s): Kodama S, Fujihara K, Ishiguro H, Horikawa C, Ohara N, Yachi Y, Tanaka S, Shimano H, Kato K, Hanyu O, Sone H
  • Journal Title: Am J Surg Pathol Volume: 11 Issue: 11 Pages: 816-818
  • DOI: 10.1016/j.annepidem.2016.09.004
  • Peer Reviewed / Open Access
• [Journal Article] Utility of nonblood-based risk assessment for predicting type 2 diabetes mellitus: A meta-analysis (2016)
  • Author(s): Yoshizawa S, Kodama S, Fujihara K, Ishiguro H, Ishizawa M, Matsubayashi Y, MatsunagaS, Yamada T, Shimano H, Kato K, Hanyu O, Sone H
  • Journal Title: Prev Med Volume: 91 Pages: 180-187
  • DOI: 10.1016/j.ypmed.2016.07.026
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of clinical characteristics in patients with type 2 diabetes among whom different antihyperglycemic agents were prescribed as monotherapy or combination therapy by diabetes specialists. (2016)
  • Author(s): Fujihara K, Hanyu O, Heianza Y, Suzuki A, Yamada T, Yokoyama H, Tanaka S, Yagyu H, Shimano H, Kashiwagi A, Yamazaki K, Kawai K, Sone H.
  • Journal Title: J Diabetes Investig Volume: 7 Issue: 2 Pages: 260-9
  • DOI: 10.1111/jdi.12387
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] In Search of the Ideal Resistance Training Program to Improve Glycemic Control and its Indication for Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. (2016)
  • Author(s): Ishiguro H, Kodama S, Horikawa C, Fujihara K, Hirose AS, Hirasawa R, Yachi Y, Ohara N, Shimano H, Hanyu O, Sone H.
  • Journal Title: Sports Med. Volume: 46(1):67-77. Issue: 1 Pages: 67-77
  • DOI: 10.1007/s40279-015-0379-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Meta-analytic research on the relationship between cumulative risk alleles and risk of type 2 diabetes mellitus (2016)
  • Author(s): Kodama S, Fujihara K, Ishiguro H, Horikawa C, Ohara N, Yachi Y, Tanaka S, Shimano H, Kato K, Hanyu O, Sone H
  • Journal Title: Diabetes/metabolism research and reviews Volume: 32 Issue: 2 Pages: 178-186
  • DOI: 10.1002/dmrr.2680
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Risk of the Development of Type 2 Diabetes in Relation to Overall Obesity, Abdominal Obesity and the Clustering of Metabolic Abnormalities in Japanese Individuals - Does Metabolically Healthy Overweight Really Exist?: Niigata Wellness Study (2015)
  • Author(s): Heianza Y, Kato K, Kodama S, Ohara N, Suzuki A, Tanaka S, Hanyu O, Sato K, Sone H
  • Journal Title: Diabet Med Volume: 32 Issue: 5 Pages: 665-72
  • DOI: 10.1111/dme.12646
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A possible link between BDNF and mTOR in control of food intake. (2014)
  • Author(s): Takei N, Furukawa K, Hanyu O, Sone H, Nawa H.
  • Journal Title: Front Psychol Volume: 5 Pages: 1093-1093
  • DOI: 10.3389/fpsyg.2014.01093
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] mTOR signaling and its roles in normal and abnormal brain development. (2014)
  • Author(s): Takei N and Nawa H.
  • Journal Title: Front Mol Neurosci. Volume: 7 Pages: 28-28
  • DOI: 10.3389/fnmol.2014.00028
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Impact on short-term glycaemic control of initiating diabetes care versus leaving diabetes untreated among individuals with newly screening-detected diabetes in Japan (2014)
  • Author(s): Heianza Y, Suzuki A, Fujihara K, Tanaka S, Kodama S, Hanyu O, Sone H.
  • Journal Title: Journal of epidemiology and community health Volume: 68 Issue: 12 Pages: 1189-1195
  • DOI: 10.1136/jech-2014-204054
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Stability and changes in metabolically healthy overweight or obesity and risk of future diabetes: Niigata wellness study (2014)
  • Author(s): Heianza Y, Kato K, Kodama S, Suzuki A, Tanaka S, Hanyu O, Sato K, Sone H.
  • Journal Title: Obesity (Silver Spring) Volume: 22 Issue: 11 Pages: 2420-2425
  • DOI: 10.1002/oby.20855
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of sleep duration as a risk factor for Type 2 diabetes among adults of different ages in Japan: the Niigata Wellness Study (2014)
  • Author(s): Heianza Y, Kato, K, Fujihara, K, Tanaka, S, Kodama, S, Hanyu O, Sato K, Sone H.
  • Journal Title: Diabetic Medicine Volume: 31 Issue: 11 Pages: 1363-1367
  • DOI: 10.1111/dme.12555
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] High Risk of Failing Eradication of Helicobacter Pylori in Patients with Diabetes: A Meta-analysis (2014)
  • Author(s): Horikawa C, Kodama S, Fujihara K, Hirasawa R, Yachi Y, Suzuki A, Hanyu O, Shimano H, Sone H
  • Journal Title: Diabet Res Clin Prac Volume: 106 Issue: 1 Pages: 81-7
  • DOI: 10.1016/j.diabres.2014.07.009
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dietary Sodium Intake and Incidence of Diabetes Complications in Japanese Patients with Type 2 Diabetes: Analysis of the Japan Diabetes Complications Study (JDCS) (2014)
  • Author(s): Horiakwa C, Yoshimura Y, Kamada C, Tanaka S, Tanaka S, Hanyu O, Araki A, Ito H, Tanaka A, Ohashi Y, Akanuma Y, Yamada N, Sone H
  • Journal Title: J Clin Endocrinol Metab Volume: 99 Issue: 10 Pages: 3635-43
  • DOI: 10.1210/jc.2013-4315
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dietary intake in Japanese patients with type 2 diabetes: Analysis from Japan Diabetes Complications Study (2014)
  • Author(s): Horikawa C, Yoshimura Y, Kamada C, Tanaka S, Tanaka S, Takahashi A, Hanyu O, Araki A, Ito H, TanakaA, Ohashi Y, Akanuma Y, Yamada N, Sone H
  • Journal Title: J Diabet Invest Volume: 5 Issue: 2 Pages: 176-87
  • DOI: 10.1111/jdi.12146
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparison of different aspects of BMI history to identify undiagnosed diabetes in Japanese men and women: Toranomon Hospital Health Management Center Study 12 (TOPICS 12) (2014)
  • Author(s): Yoshizawa S, Heianza Y, Arase Y, Saito K, Hsieh SD, Tsuji H, Hanyu O, Suzuki A, Tanaka S, Kodama S, Shimano H, Hara S, Sone H.
  • Journal Title: Diabetic Medicine Volume: 31 Issue: 11 Pages: 1378-1386
  • DOI: 10.1111/dme.12471
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 最終糖化産物(AGE)はヒト血小板からSrc family kinaseの活性を介してBDNFの放出を促進させる. (2016)
  • Author(s): 古川和郎、武井延之、岩倉百合子、外山英和、羽入修、布施一郎、那波宏之、曽根博仁.
  • Organizer: 第59回日本糖尿病学会年次学術集会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
• [Presentation] Distance between dietary intake and self-rated dietary behavior in patients with diabetes: analysis from National Health and Nutrition survey in Japan. (2016)
  • Author(s): Horikawa C MN, Tsuruta M, Oshikane Y, Hirasawa R, Yachi Y, Fujihara K, Hanyu O, Sone H
  • Organizer: European Association for the Study of Diabetes(EASD)
  • Place of Presentation: Munich（Germany）
  • Int'l Joint Research
• [Presentation] Body Mass Index (BMI), Waist Circumference (WC) and Waist Height Ratio (WHtR) Cutoff Values, and the Impact of Their Combinations on Future Diabetes among Japanese Individuals. (2016)
  • Author(s): Igarashi R FK, Heianza Y, Ishizawa M, Tsuruta M, Hatta M, Yoshizawa S, Horikawa C, Matsunaga S, Hanyu O, Kodama S, Sato K, Kato K, Sone.
  • Organizer: 76th American Diabetes Association Scientific Sessions (ADA)
  • Place of Presentation: New Orleans（USA）
  • Int'l Joint Research
• [Presentation] Association of Physical Activity and Neighborhood Environment in Japanese Patients with Type 2 Diabetes: An Observational Study in Multiple Institutes across Japan (JDDM). (2016)
  • Author(s): Yoshizawa S FK, Heianza Y, Tsuruta M, Kato K, Matsunaga S, Kodama S, Hanyu O, Kawai K, Kurihara K, Maekawa S, Sone H.
  • Organizer: 76th American Diabetes Association Scientific Sessions (ADA)
  • Place of Presentation: New Orleans（USA）
  • Int'l Joint Research
• [Presentation] Is Carbohydrate Intake Associated with the Incidence of Diabetes Complications? Japan Diabetes Complication Study (JDCS). (2016)
  • Author(s): Horikawa C YY, Kameda C, Tanaka S, Tanaka S, Hanyu O, Araki A, Ito, H, Tanaka A, Ohashi Y, Akanuma Y, Yamada N, Sone H.
  • Organizer: 76th American Diabetes Association Scientific Sessions (ADA)
  • Place of Presentation: New Orleans（USA）
  • Int'l Joint Research
• [Presentation] Risk of development of dysglycemia according to the combination of obesity and degrees of metabolic abnormalities. (2015)
  • Author(s): Heianza Y, Kato K, Kodama S, Tashiro M, Hanyu O, Sato K, Sone H.
  • Organizer: International Diabetes Fereration (IDF) 2015
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2015-11-30
  • Int'l Joint Research
• [Presentation] Metabolic health, obesity and the risk of developing chronic kidney disease among Japanese individuals. (2015)
  • Author(s): Heianza Y, Kato K, Kodama S, Tashiro M, Hanyu O, Sato K, Sone H.
  • Organizer: International Diabetes Fereration (IDF) 2015
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2015-11-30
  • Int'l Joint Research
• [Presentation] Assessment of Kidney Dysfunction with Cystatin C- and Creatinine-based Estimated Glomerular Filtration Rate and Predicting Future Type 2 Diabetes among Japanese: Toranomon Hospital Health Management Center Study. (2015)
  • Author(s): Heianza Y, Hara S, Kodama S, Saito K, Tanaka S, Hanyu O, Kobayashi T, Arase Y, Sone H.
  • Organizer: 75th American Diabetes Association Scientific Sessions(ADA)
  • Place of Presentation: Boston, USA
  • Year and Date: 2015-06-05
  • Int'l Joint Research
• [Presentation] Family History of Diabetes, Presence or Absence of Metabolic Risk Factors, and 5-Year Incident Risk of Type 2 Diabetes in Japanese Men: Toranomon Hospital Health Management Center Study. (2015)
  • Author(s): Igarashi R, Heianza Y, Kodama S, Hatta M, Saito K, Hanyu O, Hara S, Kobayashi T, Arase Y, Sone H.
  • Organizer: 75th American Diabetes Association Scientific Sessions(ADA)
  • Place of Presentation: Boston, USA
  • Year and Date: 2015-06-05
  • Int'l Joint Research
• [Presentation] Longitudinal Trajectories of Glucose, Insulin Sensitivity, and Insulin Secretion during Development of Type 2 Diabetes in Japanese: Toranomon Hospital Health Management Center Study. (2015)
  • Author(s): Heianza Y, Fujihara K, Hara S, Hanyu O, Saito K, Tanaka S, Kodama S, Kobayashi T, Arase Y, Sone H.
  • Organizer: 75th American Diabetes Association Scientific Sessions(ADA)
  • Place of Presentation: Boston, USA
  • Year and Date: 2015-06-05
  • Int'l Joint Research
• [Presentation] Characteristics of diabetic complications in Japanese patients. 50th European Association for the Study of Diabetes. (2014)
  • Author(s): Sone H
  • Organizer: 50th European Association for the Study of Diabetes.
  • Place of Presentation: Reed Messe Vienna（オーストリア）
  • Year and Date: 2014-09-15
• [Presentation] Characteristics of patients with type 2 diabetes who achieved better glycemic control through resistance training: A meta-analysis. (2014)
  • Author(s): Ishiguro H, Kodama S, Mtsunaga S, Horikawa C, Heianza Y, Ohara N, Yamada T, Suzuki T, Hanyu O, Sone H.
  • Organizer: 50th European Association for the Study of Diabetes.
  • Place of Presentation: Reed Messe Vienna（オーストリア）
  • Year and Date: 2014-09-15
• [Presentation] Metabolically Healthy Obesity, Presence or Absence of Fatty Liver, and Risk of Type 2 Diabetes in Japanese Individuals. (2014)
  • Author(s): Heianza Y, Arase Y, Tsuji H, Fujihara K, Saito K, Hsieh SD, Tanaka S, Kodama S, Hara S, Sone H.
  • Organizer: 50th European Association for the Study of Diabetes.
  • Place of Presentation: Reed Messe Vienna（オーストリア）
  • Year and Date: 2014-09-15
• [Presentation] Limitation of Risk Value in Persons at Genetically High Risk of Diabetes mellitus-Meta-analytic Research. (2014)
  • Author(s): Kodama S, Horikawa C, Fujihara K, Heianza Y, Yachi Y, Tanaka S, Ohara N, Suzuki A, Hanyu O, Sone H.
  • Organizer: 74th American Diabetes Association Scientific Sessions.
  • Place of Presentation: Moscone Center（米国）
  • Year and Date: 2014-06-09
• [Presentation] Resistance Exercise Was Effective in Improving Glycemic Control but Inferior to Aerobic Exercise for Patients with Type 2 Diabetes Mellitus―A Meta-analysis. (2014)
  • Author(s): Ishiguro H, Kodama S, Horikawa C, Suzuki H, Matsunaga S, Heianza Y, Yamada T, Suzuki A, Hanyu O, Sone H.
  • Organizer: 74th American Diabetes Association Scientific Sessions.
  • Place of Presentation: Moscone Center（米国）
  • Year and Date: 2014-06-09
• [Presentation] Risk of Development of Type 2 Diabetes by Overall Obesity, Abdominal Obesity, and Metabolic Abnormalities_Does Metabolically Healthy Obesity Really Exist? (2014)
  • Author(s): Heianza Y, Kato K, Suzuki A, Horikawa C, Matsunaga S, Yoshizawa S, Hanyu O, Kodama S, Sato K, Sone H.
  • Organizer: 74th American Diabetes Association Scientific Sessions.
  • Place of Presentation: Moscone Center（米国）
  • Year and Date: 2014-06-09
• [Presentation] Diabetes Risk Related to Carrying 1 Risk Allele of a Diabetes-Susceptible Gene Is Comparable to That Related to 1 Unit of Increased Body Mass Index: A Meta-analysis. (2014)
  • Author(s): Horikawa C, Kodama S, Matsunaga S, Yoshizawa S, Heiznza Y, Yachi Y, Ohara N, Suzuki A, Hanyu O, Sone H.
  • Organizer: 74th American Diabetes Association Scientific Sessions.
  • Place of Presentation: Moscone Center（米国）
  • Year and Date: 2014-06-09
• [Presentation] Stability and Changes in the Metabolically Healthy Overweight or Obese State and the Risk of Development of Future Type 2 Diabetes. (2014)
  • Author(s): Heianza Y, Suzuki A, Kato K, Fujihara K, Yamada T, Hanyu O, Kodama S, Sato K, Sone H.
  • Organizer: 74th American Diabetes Association Scientific Sessions.
  • Place of Presentation: Moscone Center（米国）
  • Year and Date: 2014-06-09
• [Book] Annual Review 糖尿病・代謝・内分泌2016 3.生活習慣と糖尿病合併症. (2016)
  • Author(s): 松永佐澄志、田中司朗、曽根博仁
  • Total Pages: 6
  • Publisher: 中外医学社
• [Book] 内分泌・糖尿病・代謝内科 「解説」テーマ3脳心血管病予防に関する包括的リスク管理チャート (2016)
  • Author(s): 羽入修、曽根博仁
  • Total Pages: 6
  • Publisher: 科学評論社
• [Book] 大血管・最小血管合併症のリスク評価-JDCS/J-EDIT リスクエンジン. 糖尿病学2015 (2015)
  • Author(s): 田中司郎、曽根博仁
  • Total Pages: 7
  • Publisher: 診断と治療社
• [Book] 糖尿病大血管症の成因・疫学．糖尿病学 (2015)
  • Author(s): 五十嵐智雄、羽入修、曽根博仁
  • Total Pages: 16
  • Publisher: 西村書店
• [Book] 新スタンダード栄養・食物シリーズ4 疾病の成り立ち 13.2糖尿病 (2015)
  • Author(s): 曽根博仁
  • Total Pages: 11
  • Publisher: 東京化学同人
• [Book] 新体系 看護学全書 人体の構造と機能② 栄養生化学. 第3章 糖質の栄養生化学 (2014)
  • Author(s): 曽根博仁
  • Total Pages: 17
  • Publisher: メヂカルフレンド社
• [Book] メディカルフィットネスQ&A (2014)
  • Author(s): 藤原和哉、児玉暁、曽根博仁
  • Total Pages: 6
  • Publisher: 社会保険研究所
• [Book] はじめて学ぶ健康・スポーツ科学シリーズ8 スポーツ医学 (2014)
  • Author(s): 児玉暁、曽根博仁
  • Total Pages: 16
  • Publisher: 化学同人
• [Book] Characteristics of Prediabetes/Diabetes and Prevention Initiatives in East Asia. Global Health Perspectives in Prediabetes and Diabetes Prevention. (2014)
  • Author(s): Sone H
  • Total Pages: 63
  • Publisher: World Scientific
• [Remarks] 新潟大学医学部・大学院医歯学総合研究科 血液・内分泌・代謝内科学分野ホームページ
  • URL: http://www.med.niigata-u.ac.jp/emh/results.html