Elucidation of the pathophysiological roles of thyroid hormone metabolism in diabetes mellitus

• Project/Area Number: 26293125
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Gunma University
• Principal Investigator: Murakami Masami 群馬大学, 医学(系)研究科(研究院), 教授 (30241871)
• Co-Investigator(Kenkyū-buntansha): 角野 博之 群馬大学, 医学部附属病院, 講師 (10375579) ; 常川 勝彦 群馬大学, 医学(系)研究科(研究院), 助教 (30436307) ; 奈良 誠人 群馬大学, 医学部附属病院, 助教 (80420165) ; 荒木 修 群馬大学, 医学部附属病院, 助教 (80589482) ; 木村 孝穂 群馬大学, 医学(系)研究科(研究院), 講師 (90396656) ; 荻原 貴之 群馬大学, 医学部附属病院, 助教 (80361377)
• Co-Investigator(Renkei-kenkyūsha): OKU Hiroyuki 群馬大学, 理工学研究院, 准教授 (20301749)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000); Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
• Keywords: 糖尿病 / 甲状腺ホルモン / 遺伝子 / 一塩基多型 / 自己抗体 / 動脈硬化

Outline of Final Research Achievements

We have studied the expression and regulation of thyroid hormone metabolism, including type 2 iodothyronine deiodinase (D2) which activates thyroid hormones and type 3 iodothyronine deiodinase (D3) which inactivates thyroid hormones.
We found the expression of D3 in cultured pancreatic beta cells, which is stimulated by GLP-1 via a cAMP-PKA mediated pathway. D3 is suggested to increases insulin secretion from pancreatic beta cells by decreasing intracellular T3. Furthermore, we discovered the expression of D2 in cultured human umbilical vein endothelial cells (HUVECs). Conversion of T4 to T3 by D2 is required for rapid nongenomic action of T4, which results in migration of HUVECs.
These results may open a novel perspective on understanding of the mechanisms of thyroid hormone action.

Research Products

• [Int'l Joint Research] University of California Los Angeles/Vanderbilt University/Cornell University(米国)
• [Int'l Joint Research] Monash University(オーストラリア)
• [Int'l Joint Research] Finsen Laboraotory/University of Copenhagen(デンマーク)
• [Int'l Joint Research] University of Montreal(カナダ)
• [Int'l Joint Research] Universite de Lyon(フランス)
• [Int'l Joint Research]
• [Int'l Joint Research] Cesar Milstein Hospital/INFIBIOC-University of Buenos Aires(Argentina)
• [Journal Article] Comparison of 16S ribosomal RNA gene sequence analysis and conventional culture in the environmental survey of a hospital. (2017)
  • Author(s): Manaka A, Tokue Y, Murakami M.
  • Journal Title: J Pharm Health Care Sci. Volume: - Issue: 1
  • DOI: 10.1186/s40780-017-0074-y
  • Peer Reviewed / Open Access
• [Journal Article] Lipoprotein lipase does not increase significantly in the postprandial plasma. (2017)
  • Author(s): Ishiyama N, Sakamaki K, Shimomura Y, Kotani K, Tsuzaki K, Sakane N, Miyashita K, Fukamachi I, Kobayashi J, Stanhope KL, Havel PJ, Kamachi K, Tanaka A, Tokita Y, Machida T, Murakami M, Nakajima K.
  • Journal Title: Clinica Chimica Acta Volume: 464 Pages: 204-210
  • DOI: 10.1016/j.cca.2016.11.035
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Triglyceride content in remnant lipoproteins is significantly increased after food intake and is associated with plasma lipoprotein lipase. (2017)
  • Author(s): Nakajima K, Tokita Y, Sakamaki K, Shimomura Y, Kobayashi J, Kamachi K, Tanaka A, Stanhope KL, Havel PJ, Wang T, Machida T, Murakami M.
  • Journal Title: Clinica Chimica Acta Volume: 465 Pages: 45-52
  • DOI: 10.1016/j.cca.2016.12.011
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Monoclonal antibodies that bind to the Ly6 domain of GPIHBP1 abolish the binding of LPL. (2017)
  • Author(s): Hu X, Sleeman MW, Miyashita K, Linton MF, Allan CM, He C, Larsson M, Tu Y, Sandoval NP, Jung RS, Mapar A, Machida T, Murakami M, Nakajima K, Ploug M, Fong LG, Young SG, Beigneux AP.
  • Journal Title: JOURNAL OF LIPID RESEARCH Volume: 58 Pages: 208-215
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Use of capillary electrophoresis with dual-opposite end injection for simultaneous analysis of small ions in saliva samples from wrestlers undergoing a weight training program. (2016)
  • Author(s): Mori M, Ishikawara F, Tomoda T, Yamada S, Okamoto M, Itabashi H, Seki Y, Matsumoto R, Shoho Y, Martha L, Sumino H, Murakami M.
  • Journal Title: JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES Volume: 15 Pages: 1012-1013
  • Peer Reviewed
• [Journal Article] The majority of lipoprotein lipase in plasma is bound to remnant lipoproteins: A new definition of remnant lipoproteins. (2016)
  • Author(s): Sato K, Okajima F, Miyashita K, Imamura S, Kobayashi J, Stanhope KL, Havel PJ, Machida T, Sumino H, Murakami M, Schaefer E, Nakajima K.
  • Journal Title: Clin Chim Acta Volume: 461 Pages: 114-125
  • DOI: 10.1016/j.cca.2016.06.020
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An LPL-specific monoclonal antibody, 88B8, that abolishes the binding of LPL to GPIHBP1. (2016)
  • Author(s): Allan CM, Larsson M, Hu X, He C, Jung RS, Mapar A, Voss C, Miyashita K, Machida T, Murakami M, Nakajima K, Bensadoun A, Ploug M, Fong LG, Young SG, Beigneux AP
  • Journal Title: JOURNAL OF LIPID RESEARCH Volume: 57 Issue: 10 Pages: 1889-1898
  • DOI: 10.1194/jlr.m070813
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Biological Antioxidant Potential Negatively Correlates With Carotid Artery Intima-Media Thickness (2016)
  • Author(s): Yagi H, Sumino H, Yoshida K, Aoki T, Tsunekawa K, Araki O, Kimura T, Nara M, Nakajima K, Murakami M
  • Journal Title: International Heart Journal Volume: 57 Issue: 2 Pages: 220-225
  • DOI: 10.1536/ihj.15-389
  • NAID: 130005139772
  • ISSN: 1349-2365, 1349-3299
  • Peer Reviewed / Open Access
• [Journal Article] Fasting serum insulin levels and insulin resistance are associated with blood rheology in Japanese young adults without diabetes. (2016)
  • Author(s): Yoshida K, Kimura T, Aoki T, Tsunekawa K, Araki O, Shoho Y, Nara M, Sumino H, Murakami M.
  • Journal Title: J Int Med Res Volume: 44 Issue: 3 Pages: 496-507
  • DOI: 10.1177/0300060515627561
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Atherogenic lipoprotein in subclinical hypothyroidism and their relationship with hepatic lipase activity: response to replacement treatment with levothyroxine. (2016)
  • Author(s): Brenta G, Berg G, Miksztowics V, Lopez G, Lucero D, Faingold C, Murakami M, Machida T, Nakajima K, Schreier L.
  • Journal Title: Thyroid Volume: 26 Issue: 3 Pages: 365-372
  • DOI: 10.1089/thy.2015.0140
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Type 2 Iodothyronine Deiodinase Activity Is Required for Rapid Stimulation of PI3K by Thyroxine in Human Umbilical Vein Endothelial Cells. (2015)
  • Author(s): Aoki T, Tsunekawa K, Araki O, Ogiwara T, Nara M, Sumino H, Kimura T, Murakami M.
  • Journal Title: Endocrinology Volume: 156 Issue: 11 Pages: 4312-4324
  • DOI: 10.1210/en.2014-1988
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Impaired blood rheology is associated with endothelial dysfunction in patients with coronary risk factors. (2015)
  • Author(s): Yagi H, Sumino H, Aoki T, Tsunekawa K, Araki O, Kimura T, Nara M, Ogiwara T, Murakami M.
  • Journal Title: Clin Hemorheol Microcirc. Volume: 62 Issue: 2 Pages: 139-150
  • DOI: 10.3233/ch-151960
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The role of circulating lipoprotein lipase and adiponectin on the particle size of remnant lipoproteins in patients with diabetes mellitus and metabolic syndrome (2015)
  • Author(s): Shirakawa T, Nakajima K, Yatsuzuka SI, Shimomura Y, Kobayashi J, Machida T, Sumino H, Murakami M
  • Journal Title: Clinica Chimica Acta Volume: 440 Pages: 123-132
  • DOI: 10.1016/j.cca.2014.10.029
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of the effect of post-heparin and pre-heparin lipoprotein lipase and hepatic triglyceride lipase on remnant lipoprotein metabolism (2015)
  • Author(s): Shirakawa T, Nakajima K, Shimomura Y, Kobayashi J, Stanhope K, Havel P, Machida T, Sumino H, Murakami M
  • Journal Title: Clinica Chimica Acta Volume: 440 Pages: 193-200
  • DOI: 10.1016/j.cca.2014.07.020
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between carotid artery intima-media thickness and small dense low-density lipoprotein cholesterol concentrations measured by homogeneous assay in Japanese subjects (2015)
  • Author(s): Aoki T, Yagi H, Sumino H, Tsunekawa K, Araki O, Kimura T, Nara M, Ogiwara T, Nakajima K, Murakami M
  • Journal Title: Clin Chim Acta Volume: 442 Pages: 110-114
  • DOI: 10.1016/j.cca.2015.01.010
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Determination of serum lipoprotein lipase using a latex particle-enhanced turbidimetric immunoassay with an automated analyzer (2015)
  • Author(s): Machida T, Miyashita K, Sone T, Tanaka S, Nakajima K, Saito M, Stanhope K, Havel P, Sumino H, Murakami M
  • Journal Title: Clin Chim Acta Volume: 442 Pages: 130-135
  • DOI: 10.1016/j.cca.2015.01.016
  • Peer Reviewed / Open Access
• [Journal Article] Frequency and clinical implication of the R450H mutation in the thyrotropin receptor gene in the Japanese population detected by Smart Amplification Process 2 (2014)
  • Author(s): Tsunekawa K, Yanagawa Y, Aoki T, Morimura T, Araki O, Kimura T, Ogiwara T, Kotajima N, Yanagawa M, Murakami M
  • Journal Title: Biomed Res Int Volume: 2014 Pages: 964635-964635
  • DOI: 10.1155/2014/964635
  • Peer Reviewed / Open Access
• [Journal Article] Glucagon-like peptide-1 stimulates type 3 iodothyronine deiodinase expression in a mouse isulinoma cell line (2014)
  • Author(s): Akiyama S, Ogiwara T, Aoki T, Tsunekawa K, Araki O, Murakami M
  • Journal Title: Life Sci Volume: 115 Issue: 1-2 Pages: 22-28
  • DOI: 10.1016/j.lfs.2014.09.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Small dense LDL cholesterol measured by homogeneous assay in Japanese healthy controls, metabolic syndrome and diabetes patients with or without a fatty liver (2014)
  • Author(s): Kikkawa K, Nakajima K, Shimomura Y, Tokita Y, Machida T, Sumino H, Murakami M
  • Journal Title: Clin Chim Acta Volume: 438 Pages: 70-79
  • DOI: 10.1016/j.cca.2014.07.017
  • Peer Reviewed / Open Access
• [Presentation] Assesment of the glucose tolerance among young Japanese subjects by the shape of plasma glucose concentration curve during OGTT (2016)
  • Author(s): Aoki T, Kimura T, Tsunekawa K, Araki O, Nara M, Yoshida A, Machida T, Murakami M
  • Organizer: The 32nd World Congress of Biomedical Laboratory Science
  • Place of Presentation: Kobe
  • Year and Date: 2016-08-31
  • Int'l Joint Research
• [Presentation] The sodium glucose co-transporter 2 receptor inhibitors attenuated the results leukocytes tested by urine dipsticks (2016)
  • Author(s): Kamiyama K, Machida T, Yoshida A, Araki O, Kimura T, Murakami M
  • Organizer: The 32nd World Congress of Biomedical Laboratory Science
  • Place of Presentation: Kobe
  • Year and Date: 2016-08-31
  • Int'l Joint Research
• [Presentation] Evaluation of free and toral prostate-specific antigen assay on the AIA-CL2400 analyzer (2016)
  • Author(s): Iwai M, Nakajima K, Kamiyama K, Fujii S, Machida T, Araki O, Ito K, Murakami M
  • Organizer: The 32nd World Congress of Biomedical Laboratory Science
  • Place of Presentation: Kobe
  • Year and Date: 2016-08-31
  • Int'l Joint Research
• [Presentation] Changes in gender preference of female patients for repeated transthoracic echocardiography (2016)
  • Author(s): Okada K, Kurosawa K, Kimura T, Niwa K, Ikoma T, Morita K, Machida T, Murakami M
  • Organizer: The 32nd World Congress of Biomedical Laboratory Science
  • Place of Presentation: Kobe
  • Year and Date: 2016-08-31
  • Int'l Joint Research
• [Presentation] Evaluation of the coagulation factor VIII and IX activity measurement using the chromogenic reagent (2016)
  • Author(s): Inoue M, Shizuka R, Sato A, Hayakawa M, Machida T, Tsunekawa K, Koiso H, Murakami M
  • Organizer: The 32nd World Congress of Biomedical Laboratory Science
  • Place of Presentation: Kobe
  • Year and Date: 2016-08-31
  • Int'l Joint Research
• [Presentation] Thyroid hormone action – update (2016)
  • Author(s): Murakami M, Aoki T, Tsunekawa K, Araki O, Nara M, Sumino H, Kimura T
  • Organizer: 第14回アジア臨床病理臨床検査医学会
  • Place of Presentation: 台湾・台北
  • Year and Date: 2016-03-25
  • Int'l Joint Research / Invited
• [Presentation] 臨床検査領域におけるグローバル化の推進 日本臨床検査医学会における国際化の取り組み (2015)
  • Author(s): 村上正巳、山田俊幸
  • Organizer: 第62回日本臨床検査医学会学術集会
  • Place of Presentation: 岐阜県岐阜市
  • Year and Date: 2015-11-19
  • Invited
• [Presentation] ヒトオリゴデンドログリオーマ(HOG)細胞における甲状腺ホルモン代謝機構の解析 (2015)
  • Author(s): 荒木 修, 荻原 貴之, 石垣 宏尚, 牛木 和美, 正保 佳史, 青木 智之, 常川 勝彦, 木村 孝穂, 奈良 誠人, 角野 博之, 村上 正巳
  • Organizer: 第58回日本甲状腺学会学術集会
  • Place of Presentation: 福島県福島市
  • Year and Date: 2015-11-05
• [Presentation] 甲状腺刺激ホルモン(TSH)測定値のハーモナイゼーション (2015)
  • Author(s): 竹岡 啓子, 日高 洋, 菱沼 昭, 池田 勝義, 大久保 滋夫, 土屋 達行, 橋口 照人, 堀田 多恵子, 古田 耕, 松下 一之, 松本 祐之, 村上 正巳, 前川 真人
  • Organizer: 第58回日本甲状腺学会学術集会
  • Place of Presentation: 福島県福島市
  • Year and Date: 2015-11-05
• [Presentation] Current issues in laboratory medicine (2015)
  • Author(s): Murakami M
  • Organizer: 第14回インドネシア臨床病理臨床検査医学会
  • Place of Presentation: インドネシア・マナド
  • Year and Date: 2015-10-22
  • Int'l Joint Research / Invited
• [Presentation] 微量臨床検体におけるSmartAmp法の検出感度の解析 (2014)
  • Author(s): 正保 佳史, 常川 勝彦, 関口 拓磨, 青木 智之, 荒木 修, 木村 孝穂, 奈良 誠人, 荻原 貴之, 矢部 茂季, 町田 哲男, 村上 正巳
  • Organizer: 第61回日本臨床検査医学会
  • Place of Presentation: 福岡
  • Year and Date: 2014-11-22 – 2014-11-25
• [Presentation] ヒト褐色脂肪と2型甲状腺ホルモン脱ヨード化酵素(DIO2)の一塩基多型 (2014)
  • Author(s): 米代 武司, 松下 真美, 正保 佳史, 常川 勝彦, 村上 正巳, 斉藤 昌之
  • Organizer: 第35回日本肥満学会
  • Place of Presentation: 宮崎
  • Year and Date: 2014-10-24 – 2014-10-25
• [Presentation] Clinical implication of aporipoprotein M: apolipoprotein M may be a biomarker of coagulation and fibrinolysis (2014)
  • Author(s): Aoki Ｔ, Kimura Ｔ, Sｈimizu Ｔ, Sumino Ｈ, Miyazaki Ｏ, Fukamachi Ｉ, Nakajima Ｋ, Okajima Ｆ, Murakami Ｍ
  • Organizer: 第82回欧州動脈硬化学会
  • Place of Presentation: マドリッド
  • Year and Date: 2014-05-31 – 2014-06-03
• [Presentation] マウス膵β細胞由来MIN6細胞におけるGLP-1刺激による3型甲状腺ホルモン脱ヨード酵素(D3)の発現 (2014)
  • Author(s): 秋山 滋男, 荻原 貴之, 青木 智之, 常川 勝彦, 荒木 修, 村上 正巳
  • Organizer: 第57回日本糖尿病学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] Association between the effect of physical exercise in glucose matabolism and the polymorphism of type 2 iodothyronine deiodinase (2014)
  • Author(s): Tsunekawa K, Aoki T, Araki O, Ogiwara T, Kimura T, Nara M, Sumino H, Machida T, Murakami M
  • Organizer: The 9th Cherry Blossom Symposium International Conference of Clinical Laboratory Automation and Robotics
  • Place of Presentation: 横浜
  • Year and Date: 2014-04-17 – 2014-04-19
• [Book] Thyroid Hormone Disruption and Neurodevelopment (2016)
  • Author(s): Murakami M
  • Total Pages: 209
  • Publisher: Springer
• [Book] 日常診療のための検査値のみかた (2015)
  • Author(s): 村上正巳
  • Total Pages: 757
  • Publisher: 中外医学社
• [Book] 今日の臨床検査 (2015)
  • Author(s): 村上正巳
  • Total Pages: 673
  • Publisher: 南江堂
• [Book] これだけは知っておきたい検査のポイント (2015)
  • Author(s): 村上正巳
  • Total Pages: 627
  • Publisher: 医学書院
• [Book] 医学大辞典第20版 (2015)
  • Author(s): 村上正巳
  • Total Pages: 3101
  • Publisher: 南山堂
• [Book] パーフェクトガイド検査値事典 (2014)
  • Author(s): 村上正巳
  • Total Pages: 707
  • Publisher: 総合医学社
• [Remarks] 甲状腺ホルモンによる血管修復のメカニズムを解明
  • URL: http://www.gunma-u.ac.jp/information/8136