教授：櫛山　暁史（クシヤマ　アキフミ）

教授

薬物治療学

東京大学大学院医学系研究科博士課程（2006年3月）

博士（医学）（東京大学：2006年3月）

薬物治療学Ⅰ，Ⅲ，Ⅵ、症例解析演習Ⅰ，Ⅱ、臨床薬学基礎実習、事前実務実習、病院薬学コース、海外医療研修コース、薬剤師生涯学習講座、大学院薬物治療学特論・演習、生命研究倫理

インスリン抵抗性、尿酸代謝、動脈硬化、糖尿病発症機序、インスリン治療患者の意識、糖尿病と骨、糖尿病と消化管障害、心電波形の周波数解析、レセプトデータを用いた処方動向と予後、糖尿病網膜症の新規治療の開発、新規腎保護薬物の開発、Drug Repositioning、

核酸代謝と生活習慣病の関連、分泌蛋白と生活習慣病の関連、糖尿病合併症の予後規定因子、生活習慣病の薬物治療学、生活習慣病の非薬物治療学

日本糖尿病学会、日本日本分子生物学会、日本血管生物医学会、日本痛風核酸代謝学会、日本内科学会

日本成人病生活習慣病学会評議員、日本血管生物医学会評議員

薬剤師国家試験問題検討委員会、国家試験・CBT対策委員会、バイオハザード安全委員会、大学院運営委員会、労働安全委員会、学生厚生委員、RI管理委員会

日本医療機能評価機構医療事故情報等収集事業分析班委員、糖尿病専門医、内科認定医、RIZAP医療顧問、東久留米駅前クリニック顧問、博報堂メディカルアドバイザー

1. 糖尿病患者に対するMCG解析 櫛山　暁史 第57回　日本人間ドック学会学術大会／長野県：7月29日,2016年
2. 高齢者糖尿病治療について 櫛山　暁史 超高齢社会のトータルケアを考える会／東京都：2016年9月14日
3. 安全かつ効果的に結果にコミットできる減量方法の確立を目指して 櫛山　暁史第38回日本肥満学会／大阪府： 2017年10月7日
4. Gout with Diabetes Akifumi KUSHIYAMA The 3rd Experts in Asia for Gout and hyperuricemia(EAGER)／台湾・高雄市：2018年9月9日

Nakatsu Y, Matsunaga Y, Yamamotoya T, Ueda K, Inoue MK, Mizuno Y, Nakanishi M, Sano T, Yamawaki Y, Kushiyama A, Sakoda H, Fujishiro M, Ryo A, Ono H, Minamino T, Takahashi SI, Ohno H, Yoneda M, Takahashi K, Ishihara H, Katagiri H, Nishimura F, Kanematsu T, Yamada T, Asano T. Prolyl Isomerase Pin1 Suppresses Thermogenic Programs in Adipocytes by Promoting Degradation of Transcriptional Co-activator PRDM16. Cell Rep. 2019 Mar 19;26(12):3221-3230.e3. doi:10.1016/j.celrep.2019.02.066. PubMed PMID: 30893596.

Inoue MK, Yamamotoya T, Nakatsu Y, Ueda K, Inoue Y, Matsunaga Y, Sakoda H, Fujishiro M, Ono H, Morii K, Sasaki K, Masaki T, Suzuki Y, Asano T, Kushiyama A. The Xanthine Oxidase Inhibitor Febuxostat Suppresses the Progression of IgA Nephropathy, Possibly via Its Anti-Inflammatory and Anti-Fibrotic Effects in the gddY Mouse Model. Int J Mol Sci. 2018 Dec 10;19(12). pii: E3967. doi:10.3390/ijms19123967. PubMed PMID: 30544662;

Yamazaki H, Kushiyama A, Sakoda H, Fujishiro M, Yamamotoya T, Nakatsu Y, Kikuchi T, Kaneko S, Tanaka H, Asano T. Protective Effect of Sex Hormone-Binding Globulin against Metabolic Syndrome: In Vitro Evidence Showing Anti-Inflammatory and Lipolytic Effects on Adipocytes and Macrophages. Mediators Inflamm. 2018 Jun 25;2018:3062319. doi: 10.1155/2018/3062319. eCollection 2018. PubMed PMID:30046278;

Fujishiro M, Kushiyama A, Yamazaki H, Kaneko S, Koketsu Y, Yamamotoya T, Kikuchi T, Sakoda H, Suzuki R, Kadowaki T. Gastrointestinal symptom prevalence depends on disease duration and gastrointestinal region in type 2 diabetes mellitus. World J Gastroenterol. 2017 Sep 28;23(36):6694-6704. doi:10.3748/wjg.v23.i36.6694. PubMed PMID: 29085214;

Pang Z, Kushiyama A, Sun J, Kikuchi T, Yamazaki H, Iwamoto Y, Koriyama H, Yoshida S, Shimamura M, Higuchi M, Kawano T, Takami Y, Rakugi H, Morishita R, Nakagami H. Glial fibrillary acidic protein (GFAP) is a novel biomarker for the prediction of autoimmune diabetes. FASEB J. 2017 Sep;31(9):4053-4063. doi:10.1096/fj.201700110R. Epub 2017 May 25. PubMed PMID: 28546444.

Yamamotoya T, Nakatsu Y, Kushiyama A, Matsunaga Y, Ueda K, Inoue Y, Inoue MK, Sakoda H, Fujishiro M, Ono H, Kiyonari H, Ishihara H, Asano T. Trk-fused gene (TFG) regulates pancreatic β cell mass and insulin secretory activity. Sci Rep. 2017 Oct 12;7(1):13026. doi: 10.1038/s41598-017-13432-x. PubMed PMID: 29026155;

Kushiyama A, Kikuchi T, Tanaka K, Tahara T, Takao T, Onishi Y, Yoshida Y, Kawazu S, Iwamoto Y. Prediction of the effect on antihyperglycaemic action of sitagliptin by plasma active form glucagon-like peptide-1. World J Diabetes. 2016 Jun 10;7(11):230-8. doi: 10.4239/wjd.v7.i11.230. Epub 2016 Jun 11. PubMed PMID: 27326345;

Okubo H, Kushiyama A, Sakoda H, Nakatsu Y, Iizuka M, Taki N, Fujishiro M, Fukushima T, Kamata H, Nagamachi A, Inaba T, Nishimura F, Katagiri H, Asahara T, Yoshida Y, Chonan O, Encinas J, Asano T. Involvement of resistin-like molecule β
in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice. Sci Rep. 2016 Jan 28;6:20157. doi: 10.1038/srep20157. PubMed PMID: 26818807

Okubo H, Kushiyama A, Nakatsu Y, Yamamotoya T, Matsunaga Y, Fujishiro M, Sakoda H, Ohno H, Yoneda M, Asano T. Roles of Gut-Derived Secretory Factors in the Pathogenesis of Non-Alcoholic Fatty Liver Disease and Their Possible Clinical Applications. Int J Mol Sci. 2018 Oct 8;19(10). pii: E3064. doi:10.3390/ijms19103064. Review. PubMed PMID: 30297626;

Kushiyama A, Nakatsu Y, Matsunaga Y, Yamamotoya T, Mori K, Ueda K, Inoue Y, Sakoda H, Fujishiro M, Ono H, Asano T. Role of Uric Acid Metabolism-Related Inflammation in the Pathogenesis of Metabolic Syndrome Components Such as
Atherosclerosis and Nonalcoholic Steatohepatitis. Mediators Inflamm. 2016;2016:8603164. doi: 10.1155/2016/8603164. Epub 2016 Dec 14. Review. PubMed PMID: 28070145;

1: Takao T, Yanagisawa H, Suka M, Yoshida Y, Onishi Y, Tahara T, Kikuchi T, Kushiyama A, Anai M, Takahashi K, Wakabayashi Sugawa S, Yamazaki H, Kawazu S, Iwamoto Y, Noda M, Kasuga M. Synergistic association of the copper/zinc ratio under inflammatory conditions with diabetic kidney disease in patients with type 2 diabetes: The Asahi Diabetes Complications Study. J Diabetes Investig. 2021 Sep 17. doi: 10.1111/jdi.13659. Epub ahead of print. PMID: 34533892.

2: Hanaguri J, Yokota H, Watanabe M, Yamagami S, Kushiyama A, Kuo L, Nagaoka T. Retinal blood flow dysregulation precedes neural retinal dysfunction in type 2 diabetic mice. Sci Rep. 2021 Sep 15;11(1):18401. doi: 10.1038/s41598-021-97651-3. PMID: 34526573; PMCID: PMC8443656.

3: Fujishiro M, Ishihara H, Ogawa K, Murase T, Nakamura T, Watanabe K, Sakoda H, Ono H, Yamamotoya T, Nakatsu Y, Asano T, Kushiyama A. Impact of Plasma Xanthine Oxidoreductase Activity on the Mechanisms of Distal Symmetric Polyneuropathy Development in Patients with Type 2 Diabetes. Biomedicines. 2021 Aug 19;9(8):1052. doi: 10.3390/biomedicines9081052. PMID: 34440256; PMCID:PMC8391363.

4: Sugawa SW, Yoshida Y, Hikima Y, Sato H, Shimada A, Noda M, Kushiyama A. Characteristics Associated with Early Worsening of Retinopathy in Patients with Type 2 Diabetes Diagnosed with Retinopathy at Their First Visit: A Retrospective Observational Study. J Diabetes Res. 2021 Jul 17;2021:7572326. doi:
10.1155/2021/7572326. PMID: 34337073; PMCID: PMC8313317.

5: Muramatsu T, Takahashi M, Kakinuma R, Sato T, Yamamoto M, Akazawa M, Tanaka K, Kikuchi T, Kushiyama A. Decline in renal function associated with
cardiovascular autonomic neuropathy positively coordinated with proteinuria in patients with type 2 diabetes. J Diabetes Investig. 2021 Jul 6. doi:
10.1111/jdi.13625. Epub ahead of print. PMID: 34228899.

6: Matsunaga Y, Hasei S, Yamamotoya T, Honda H, Kushiyama A, Sakoda H, Fujishiro M, Ono H, Ito H, Okabe T, Asano T, Nakatsu Y. Pathological Role of Pin1 in the Development of DSS-Induced Colitis. Cells. 2021 May 17;10(5):1230. doi: 10.3390/cells10051230. PMID: 34067858; PMCID: PMC8155908.

7: Sai A, Tanaka K, Ohashi Y, Kushiyama A, Tanaka Y, Motonishi S, Sakai K, Hara S, Ozawa T. Quantitative sonographic assessment of quadriceps muscle thickness for fall injury prediction in patients undergoing maintenance hemodialysis: an observational cohort study. BMC Nephrol. 2021 May 22;22(1):191. doi:
10.1186/s12882-021-02347-5. PMID: 34022848; PMCID: PMC8140437.

8: Hasei S, Yamamotoya T, Nakatsu Y, Ohata Y, Itoga S, Nonaka Y, Matsunaga Y, Sakoda H, Fujishiro M, Kushiyama A, Asano T. Carnosic Acid and Carnosol Activate AMPK, Suppress Expressions of Gluconeogenic and Lipogenic Genes, and Inhibit Proliferation of HepG2 Cells. Int J Mol Sci. 2021 Apr 14;22(8):4040. doi: 10.3390/ijms22084040. PMID: 33919842; PMCID: PMC8070802.

9: Takahashi M, Shibasaki M, Echizen H, Kushiyama A. Comparisons between dipeptidyl peptidase-4 inhibitors and other classes of hypoglycemic drugs using two distinct biomarkers of pancreatic beta-cell function: A meta-analysis. PLoS One. 2020 Jul 24;15(7):e0236603. doi: 10.1371/journal.pone.0236603. PMID: 32706828; PMCID: PMC7380634.

10: Nakatsu Y, Yamamotoya T, Okumura M, Ishii T, Kanamoto M, Naito M, Nakanishi M, Aoyama S, Matsunaga Y, Kushiyama A, Sakoda H, Fujishiro M, Ono H, Asano T. Prolyl isomerase Pin1 interacts with adipose triglyceride lipase and negatively controls both its expression and lipolysis. Metabolism. 2021 Feb;115:154459. doi: 10.1016/j.metabol.2020.154459. Epub 2020 Dec 3. PMID: 33279499.

11: Takao T, Takahashi K, Yoshida Y, Kushiyama A, Onishi Y, Tahara T, Shimmei A, Kikuchi T, Suka M, Yanagisawa H, Iwamoto Y, Kasuga M. Effect of postprandial hyperglycemia at clinic visits on the incidence of retinopathy in patients with type 2 diabetes: An analysis using real-world long-term follow-up data. J Diabetes Investig. 2020 Jul;11(4):930-937. doi: 10.1111/jdi.13194. Epub 2020 Jan 2. PMID: 31811705; PMCID: PMC7378435.

12: Kanai N, Shono A, Kushiyama A, Akazawa M. Characteristics and Early Hypoglycemic Medications of Patients at Risk of Progression to Type 2 Diabetes
in Japan: A Retrospective Cohort Study of Health Checkup and Claims Data. Biol Pharm Bull. 2019;42(12):2016-2023. doi: 10.1248/bpb.b19-00505. PMID: 31787718.

13: Mizuno Y, Yamamotoya T, Nakatsu Y, Ueda K, Matsunaga Y, Inoue MK, Sakoda H, Fujishiro M, Ono H, Kikuchi T, Takahashi M, Morii K, Sasaki K, Masaki T, Asano T, Kushiyama A. Xanthine Oxidase Inhibitor Febuxostat Exerts an Anti-Inflammatory Action and Protects against Diabetic Nephropathy Development in KK-Ay Obese Diabetic Mice. Int J Mol Sci. 2019 Sep 21;20(19):4680. doi:10.3390/ijms20194680. PMID: 31546603; PMCID: PMC6801943.

14: Inoue MK, Matsunaga Y, Nakatsu Y, Yamamotoya T, Ueda K, Kushiyama A, Sakoda H, Fujishiro M, Ono H, Iwashita M, Sano T, Nishimura F, Morii K, Sasaki K, Masaki T, Asano T. Possible involvement of normalized Pin1 expression level and AMPK activation in the molecular mechanisms underlying renal protective effects of SGLT2 inhibitors in mice. Diabetol Metab Syndr. 2019 Jul 22;11:57. doi:10.1186/s13098-019-0454-6. PMID: 31367234; PMCID: PMC6647324.

15: Kuki A, Tanaka K, Kushiyama A, Tanaka Y, Motonishi S, Sugano Y, Furuya T, Ozawa T. Association of gait speed and grip strength with risk of cardiovascular events in patients on haemodialysis: a prospective study. BMC Nephrol. 2019 May 30;20(1):196. doi: 10.1186/s12882-019-1370-6. PMID: 31146702; PMCID: PMC6543665.

16: Ueda K, Nakatsu Y, Yamamotoya T, Ono H, Inoue Y, Inoue MK, Mizuno Y, Matsunaga Y, Kushiyama A, Sakoda H, Fujishiro M, Takahashi SI, Matsubara A,
Asano T. Prolyl isomerase Pin1 binds to and stabilizes acetyl CoA carboxylase 1 protein, thereby supporting cancer cell proliferation. Oncotarget. 2019 Feb
26;10(17):1637-1648. doi: 10.18632/oncotarget.26691. PMID: 30899433; PMCID:PMC6422191.

17: Nakatsu Y, Matsunaga Y, Yamamotoya T, Ueda K, Inoue MK, Mizuno Y, Nakanishi M, Sano T, Yamawaki Y, Kushiyama A, Sakoda H, Fujishiro M, Ryo A, Ono H, Minamino T, Takahashi SI, Ohno H, Yoneda M, Takahashi K, Ishihara H, Katagiri H, Nishimura F, Kanematsu T, Yamada T, Asano T. Prolyl Isomerase Pin1 Suppresses Thermogenic Programs in Adipocytes by Promoting Degradation of Transcriptional Co-activator PRDM16. Cell Rep. 2019 Mar 19;26(12):3221-3230.e3. doi:10.1016/j.celrep.2019.02.066. PMID: 30893596.

18: Suzuki N, Niikura R, Ihara S, Hikiba Y, Kinoshita H, Higashishima N, Hayakawa Y, Yamada A, Hirata Y, Nakata R, Okamoto M, Sano M, Kushiyama A,
Ichinose M, Woods SL, Worthley D, Iwamoto Y, Koike K. Alpha-Blockers As Colorectal Cancer Chemopreventive: Findings from a Case-Control Study, Human
Cell Cultures, and <i>In Vivo</i> Preclinical Testing. Cancer Prev Res (Phila). 2019 Mar;12(3):185-194. doi: 10.1158/1940-6207.CAPR-18-0288. Epub 2019 Jan 30. PMID: 30700439.

19: Kamatani N, Kushiyama A, Toyo-Oka L, Toyo-Oka T. Treatment of two mitochondrial disease patients with a combination of febuxostat and inosine that
enhances cellular ATP. J Hum Genet. 2019 Apr;64(4):351-353. doi: 10.1038/s10038-018-0558-0. Epub 2019 Jan 10. PMID: 30631120.

1: Inoue MK, Nakatsu Y, Yamamotoya T, Hasei S, Kanamoto M, Naitou M, Matsunaga Y, Sakoda H, Fujishiro M, Ono H, Kushiyama A, Asano T. Pin1 Plays Essential Roles in NASH Development by Modulating Multiple Target Proteins. Cells. 2019 Nov 29;8(12):1545. doi: 10.3390/cells8121545. PMID: 31795496; PMCID: PMC6952946.

2: Nakatsu Y, Yamamotoya T, Ueda K, Ono H, Inoue MK, Matsunaga Y, Kushiyama A, Sakoda H, Fujishiro M, Matsubara A, Asano T. Prolyl isomerase Pin1 in metabolic reprogramming of cancer cells. Cancer Lett. 2020 Feb 1;470:106-114. doi: 10.1016/j.canlet.2019.10.043. Epub 2019 Oct 31. PMID: 31678165.

3: Nakatsu Y, Matsunaga Y, Ueda K, Yamamotoya T, Inoue Y, Inoue MK, Mizuno Y, Kushiyama A, Ono H, Fujishiro M, Ito H, Okabe T, Asano T. Development of Pin1 Inhibitors and their Potential as Therapeutic Agents. Curr Med Chem. 2020;27(20):3314-3329. doi: 10.2174/0929867325666181105120911. PMID: 30394205.

招待講演

Novel therapeutics for diabetic retinopathy: Kushiyama A. Symposium on Interdisciplinary Approach for the Development of Novel Diagnosis and Treatment of Retinal Diseases, 2019/12, Seoul, Korea

一般講演・ポスター発表

Relationship between plaque destabilization and glucose / nucleic acid metabolism. Kushiyama A, Takahashi M and Nakagami H^a. (^aDepartment of Health Development and Medicine, Osaka University Graduate School of Medicine), Inaugural Joint Scientific Meeting of AVBS/ANZMS/AAVBM, 2019/9, Sydney, AUS

非LDLの血管障害リスク～血糖・尿酸など～：櫛山暁史、第27回血管生物医学会学術集会、2019/12、神戸

Pin1 and Trk-fused gene（TFG）：novel regulators for β-cell mass and function：山本屋 武^a、中津祐介^a、櫛山暁史、石原寿光^b、浅野知一郎^a (^a広島大学大学院医歯薬保健学研究科医化学研究室、^b日本大学医学部内科学系糖尿病代謝内科学分野) 、第62回糖尿病学会年次学術集会、2019/5、仙台

特集　糖尿病診療の”Q” 現場の疑問に答えます、pp. 842-844、Medicina　5　薬物療法（経口血糖降下薬）SGLT2阻害薬の使い方、能登洋企画、医学書院、東京 (2019)

果糖による体脂肪や中性脂肪値、尿酸値への影響について教えてください。また、適切な摂取量についても教えてください。プラクティス・セレクション6　pp. 20-22、糖尿病の療養指導Q＆A vol.2　野田光彦編集　医歯薬出版株式会社、東京　(2019)