New therapeutic strategy for brain-cardiorenal-glucose metabolism syndrome: targeting on the sympathetic nervous system and SGLT2

• Project/Area Number: 26460343
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Kagawa University
• Principal Investigator: Nishiyama Akira 香川大学, 医学部, 教授 (10325334)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 生活習慣病 / 肥満 / 糖尿病 / 腎臓病 / レニンアンジオテンシン系 / SGLT2 / インスリン抵抗性 / 血圧 / 臓器連関 / 高血圧 / 交感神経 / レニン・アンジオテンシン系 / メタボリックシンドローム

Outline of Final Research Achievements

We aimed to determine the potential roles of sympathetic nervous system, renin-angiotensin system and SGLT2 in the pathophysiology of brain-cardiorenal-glucose metabolism syndrome during the development of obese and diabetes. Our data have shown that during the development of obese and diabetes, 1) the brain-cardiorenal-glucose metabolism syndrome is exists, 2) sympathetic nervous system and intrarenal renin-angiotensin system and SGLT2 play an important role in the pathogenesis of brain-cardiorenal-glucose metabolism syndrome, 3) brain-cardiorenal-glucose metabolism syndrome contributes to the progression of diabetes cardiovascular and renal complications. These data may help to develop new strategy for diabetes cardiovascular and renal complications.

Research Products

• [Int'l Joint Research] University of California/Vanderbilt University/Tulane University(米国)
• [Journal Article] Effect of a selective SGLT2 inhibitor, luseogliflozin, on circadian rhythm of sympathetic nervous function and locomotor activities in metabolic syndrome rats. (2017)
  • Author(s): Rahman A, Fujisawa Y, Nakano D, Hitomi H, Nishiyama A.
  • Journal Title: Clin Exp Pharmacol Physiol. Volume: 44(4) Issue: 4 Pages: 522-525
  • DOI: 10.1111/1440-1681.12725
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of diuretics on sodium-dependent glucose cotransporter 2 inhibitor-induced changes in blood pressure in obese rats suffering from the metabolic syndrome. (2016)
  • Author(s): Rahman A, Kittikulsuth W, Fujisawa Y, Sufiun A, Rafiq K, Hitomi H, Nakano D, Sohara E, Uchida S, Nishiyama A.
  • Journal Title: J Hypertens. Volume: 34 Issue: 5 Pages: 893-906
  • DOI: 10.1097/hjh.0000000000000871
  • Peer Reviewed
• [Journal Article] A sodium-glucose co-transporter 2 inhibitor empagliflozin prevents abnormality of circadian rhythm of blood pressure in salt-treated obese rats. (2016)
  • Author(s): Takeshige Y, Fujisawa Y, Rahman A, Kittkulsuth W, Nakano D, Mori H, Masaki T, Ohmori K, Kohno M, Ogata H, Nishiyama A.
  • Journal Title: Hypertens. Res. Volume: 39(6) Issue: 6 Pages: 415-422
  • DOI: 10.1038/hr.2016.2
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Effect of dipeptidyl peptidase-4 inhibition on circadian blood pressure during the development of salt-dependent hypertension in rats. (2015)
  • Author(s): Sufiun A, Rafiq K, Fujisawa Y, Rahman A, Mori H, Nakano D, Kobori H, Ohmori K, Masaki T, Kohno M, Nishiyama A.
  • Journal Title: Hypertens Res. Volume: 38(4) Issue: 4 Pages: 237-243
  • DOI: 10.1038/hr.2014.173
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Role of the renal sympathetic nerve in renal glucose metabolism during the development of type 2 diabetes in rats. (2015)
  • Author(s): Rafiq K, Fujisawa Y, Sherajee SJ, Rahman A, Sufiun A, Kobori H, Koepsell H, Mogi M, Horiuchi M, Nishiyama A.
  • Journal Title: Diabetologia. Volume: 58(12) Issue: 12 Pages: 2885-2898
  • DOI: 10.1007/s00125-015-3771-9
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] SGLT2阻害薬の腎循環・機能に及ぼす直接的な影響 (2017)
  • Author(s): 西山 成、藤澤良秀、ラフマンアサダ、中野大介、人見浩史、北田研人、アンサリーチュバ
  • Organizer: 第７回日本腎臓リハビリーテーション学会
  • Place of Presentation: 筑波
  • Year and Date: 2017-02-18
• [Presentation] SGLT阻害薬は腎虚血再灌流後に生じる腎線維化の進展を抑制する (2016)
  • Author(s): 西山 成、張 一凡、人見浩史、中野大介
  • Organizer: 第20回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2016-12-15
• [Presentation] Direct responses of tubular function to acute administration of SFLT2 inhibitor in anesthetized rats (2016)
  • Author(s): 西山 成、藤澤良秀、ラフマンアサダ、中野大介、人見浩史、北田研人、アンサリチュバ
  • Organizer: 第20回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2016-12-15
• [Presentation] 食塩感受性高血圧における腎内RASの役割 (2016)
  • Author(s): 西山 成
  • Organizer: 第39回日本高血圧学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-30
  • Invited
• [Presentation] Dipping pattern of blood pressure in Dahl salt-sensitive hypertensive rats during the progression of renal injury. (2016)
  • Author(s): Sufin A, Fujisawa Y, Rahma A, Nakano D, Nishiyama A.
  • Organizer: The 17th International SHR Symposium
  • Place of Presentation: Tokyo
  • Year and Date: 2016-09-22
  • Int'l Joint Research
• [Presentation] SGLT2阻害薬の利尿作用と降圧効果 (2016)
  • Author(s): 西山 成、武重由衣、藤澤良秀、中野大介、人見浩史、Rahman A.
  • Organizer: 第16回日本抗加齢医学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-06-10
• [Presentation] 18th International Congress on Nutrition and Metabolism in Renal Disease 2016 (2016)
  • Author(s): Nishiyama A.
  • Organizer: Roles of Sympathetic Nerve and SGLT2 in the Development of Glucose Metabolism and Hypertension.
  • Place of Presentation: Naha
  • Year and Date: 2016-04-20
  • Int'l Joint Research
• [Presentation] SHR/NDmcr-cpにおけるSGLT2阻害薬の利尿作用と降圧効果 (2015)
  • Author(s): 西山 成、藤澤良秀、中野大介、ラフマンアサダ
  • Organizer: 第19回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-11
• [Presentation] A sodium-glucose co-transporter 2 inhibitor prevents abnormality of circadian rhythm of blood pressure in salt-treated obese rats. (2015)
  • Author(s): Nishiyama A, Nakano D, Ogata H, Takeshige Y
  • Organizer: American Heart Association Scientific Session
  • Place of Presentation: Orland
  • Year and Date: 2015-11-10
  • Int'l Joint Research
• [Presentation] Effects of diuretics on SGLT2 inhibitor-induced changes in blood pressure and natriuresis in obese rats suffering from the metabolic syndrome. (2015)
  • Author(s): Rahman A, Kittikulsuth W, Fujisawa Y, Hitomi H, Nakano D, Sohara E, Uchida S, Nishiyama A
  • Organizer: American Society of Nephrology
  • Place of Presentation: San Diego
  • Year and Date: 2015-11-06
  • Int'l Joint Research
• [Presentation] Changes in dipping pattern of blood pressure during the progression of renal injury in Dahl salt-sensitive hypertensive rats. (2015)
  • Author(s): Sufiun A, Fujisawa Y, Rahman A, Nakano D, Hitomi H, Nishiyama A
  • Organizer: American Heart Association High Blood Pressure Council
  • Place of Presentation: Washington DC
  • Year and Date: 2015-09-18
  • Int'l Joint Research
• [Presentation] Effect of intravenous administration of a SGLT2 inhibitor on renal hemodynamics and functions in anesthetized rats. (2015)
  • Author(s): Ansary TM、藤澤良秀、西山 成
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-06-06
• [Presentation] SGLT2阻害薬は塩分負荷した肥満OLETEラットにおいてナトリウム利尿を伴った降圧を示す (2015)
  • Author(s): 武重由依、緒方浩顕、西山 成
  • Organizer: 第44回日本心脈管作動物質学会
  • Place of Presentation: 高松
  • Year and Date: 2015-02-06 – 2015-02-07
• [Presentation] SGLT2阻害薬エンパグリフロジンは、メタボリックシンドロームラッットのdippingパターンの正常化を伴った降圧を示す (2014)
  • Author(s): 武重由依、藤澤良秀、Sufiun A、Asadur R、Rafiq K、中野大介、小堀浩幸、緒方浩顕、西山 成
  • Organizer: 第37回日本高血圧学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-10-17 – 2014-10-19
• [Presentation] Effect of SGLT2 inhibitors on circadian blood pressure in metabolic syndrome. (2014)
  • Author(s): Nishiyama A.
  • Organizer: ISN NEXUS Symposium Hypertension and Kidney
  • Place of Presentation: Brisbane
  • Year and Date: 2014-09-26 – 2014-09-28
  • Invited
• [Presentation] OLETFラットにおけるSGLT2阻害薬エンパグリフロジンの降圧作用 (2014)
  • Author(s): 武重由依、藤澤良秀、Sufiun A、Asadur R、Rafiq K、中野大介、小堀浩幸、緒方浩顕、西山 成
  • Organizer: 第57回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] Effects of a SGLT2 inhibitor empagliflozin, on blood pressure and urinary excretion of sodium in salt-treated metabolic syndrome rats. (2014)
  • Author(s): Takeshige Y,Fujisawa Y, Sufiun A, Rahman A, Rafiq K, Nakano D, Ogata H
  • Organizer: The 14th Asian Pacific Congress of Nephrology
  • Place of Presentation: Tokyo
  • Year and Date: 2014-05-15 – 2014-05-17
• [Remarks] 香川大学医学部薬理学ホームページ
  • URL: http://www.kms.ac.jp/%7Eyakuri/
• [Remarks] 香川大学医学部薬理学ホームページ
  • URL: http://www.kms.ac.jp/~yakuri/
• [Patent(Industrial Property Rights)] プロレニン受容体に対する抗体またはその抗原結合断片、およびその用途 (2016)
  • Inventor(s): 西山 成, 他
  • Industrial Property Rights Holder: 西山 成, 他
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-215385
  • Filing Date: 2016-11-02
  • Acquisition Date: 2016-12-02