Analysis of single nucleotide polymorphism in diabetes and novel mechanism for insulin secretion

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390146
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• 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): SUMINO Hiroyuki 群馬大学, 医学部附属病院, 講師 (10375579) ; TSUNEKAWA Katsuhiko 群馬大学, 大学院・医学系研究科, 助教 (30436307) ; OGIWARA Takayuki 群馬大学, 医学部附属病院, 助教 (80361377) ; ARAKI Osamu 群馬大学, 医学部附属病院, 助教 (80589482) ; KIMURA Takao 群馬大学, 大学院・医学系研究科, 講師 (90396656) ; NARA Makoto 群馬大学, 医学部附属病院, 助教 (80420165)
• Co-Investigator(Renkei-kenkyūsha): LEZHAVA Alexander 独立行政法人理化学研究所, 研究員 (40443048)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 糖尿病 / 遺伝子 / 一塩基多型 / インスリン / 甲状腺ホルモン

Research Abstract

Single nucleotide polymorphism (SNP) in type 2 iodothyronine deiodinase (D2) was found to be related to the impairment of insulin secretion and exercise induced improvement of glucose tolerance. We have indntified type 2 and type 3 iodothyronine deiodinase (D2, D3) in a mouse insulinoma cell line (MIN-6). D2 activates thyroid hormone by catalyzing conversion of T4 to T3, and D3 inactivates thyroid hormone by catalyzing conversion of T4 to rT3, and T3 to T2. Glucagon-like peptide 1 (GLP-1) stimulates D3 and D2 in MIN-6 cells. These results suggest GLP-1 regulated thyroid hormone metabolism is involved in the regulation of insulin secretion in pancreatic beta cells, which may be related to the pathophysiology of diabates mellitus.

Research Products

• [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
  • DOI: 10.1155/2014/964635.Epub2014May5
  • Peer Reviewed
• [Journal Article] Do insulin resistance conditions further impair the lipid and inflammatory profile in end-stage renal disease patients on hemodialysis? (2014)
  • Author(s): Cacciagiú L, González Al, Elbert A, De'mawrziani G, Machida T, Murakami M, López Gl, Wikinski R, Nakajima K, Schreier L
  • Journal Title: Metab Syndr Relat Disord
  • DOI: 10.1089/met.2013.0124
  • Peer Reviewed
• [Journal Article] Validation of homogeneous assays for HDL-cholesterol using fresh samples from healthy and diseased subjects (2014)
  • Author(s): Miida T, Nishimura K, Okamura T, Hirayama S, Ohmura H, Yoshida H, Miyashita Y, Ai M, Tanaka A, Sumino H, Murakami M, Inoue I, Kayamori Y, Nakamura M, Nobori T, Miyazawa Y, Teramoto T, Yokoyama S
  • Journal Title: Atherosclerosis Volume: 233 Pages: 252-259
  • DOI: 10.1016/j.atheroscclerosis.2013.12.033
  • Peer Reviewed
• [Journal Article] A critical role of fatty acid binding protein 4 and 5 (FABP4/5) in the systemic response to fasting (2013)
  • Author(s): Syamsunarno MR, Iso T, Hanaoka H, Yamaguchi A, Obokata M, Koitabashi N, Goto K, Hishiki T, Nagahata Y, Matsui H, Sano M, Kobayashi M, Kikuchi O, Sasaki T, Maeda K, Murakami M, Kitamura T, Suematsu M, Tsushima Y, Endo K, Hotamisligil GS, Kurabayashi M
  • Journal Title: PLoS One Volume: 14;8 Pages: e79386
  • DOI: 10.1371/journal.pone.0079386.eCollection2013
  • Peer Reviewed
• [Journal Article] A new enzyme-linked immunosorbent assay system for human hepatic triglyceride lipase (2013)
  • Author(s): Miyashita K, Kobayashi J, Imamura S, Kinoshita N, Stanhope KL, Havel PJ, Nakajima K, Machida T, Sumino H, Nara M, Murakami M
  • Journal Title: Clin Chim Acta Volume: 424 Pages: 201-206
  • DOI: 10.1016/j.cca.2013.06.016
  • Peer Reviewed
• [Journal Article] A novel mechanism for the inhibition of type 2 iodothyronine deiodinase by tumor necrosis factor α : involvement of proteasomal degradation (2013)
  • Author(s): Ogiwara T, Araki O, Morimura T, Tsunekawa K, Mori M, Murakami M
  • Journal Title: Endocr J Volume: 60 Pages: 1035-1045
  • DOI: 10.1507/endocrj.EJ11-0144
  • Peer Reviewed
• [Journal Article] Alterations in local thyroid hormone signaling in the hippocampus of the SAMP8 mouse at younger ages : association with delayed myelination and behavioral abnormalities (2013)
  • Author(s): Sawano E, Negishi T, Aoki T, Murakami M, Tashiro T
  • Journal Title: J Neurosci Res Volume: 91 Pages: 382-392
  • Peer Reviewed
• [Journal Article] A multicenter study on the precision and accuracy of homogeneous assays for LDL-cholesterol : comparison with a beta-quantification method using fresh serum obtained from non-diseased and diseased subjects (2012)
  • Author(s): Miida T, Nishimura K, Okamura T, Hirayama S, Ohmura H, Yoshida H, Miyashita Y, Ai M, Tanaka A, Sumino H, Murakami M, Inoue I, Kayamori Y, Nakamura M, Nobori T, Miyazawa Y, Teramoto T, Yokoyama S
  • Journal Title: Atherosclerosis Volume: 225 Pages: 208-215
  • DOI: 10.1016/j.atherosclerosis.2012.08.022
  • Peer Reviewed
• [Journal Article] The characteristics of remnant lipoproteins in the fasting and postprandial plasma (2012)
  • Author(s): Nakajima K, Nakano T, Tokita Y, Nagamine T, Yatsuzuka SI, Shimomura Y, Tanaka A, Sumino H, Nara M, Machida T, Murakami M
  • Journal Title: Clin Chim Acta Volume: 413 Pages: 1077-1086
  • DOI: 10.1016/j.cca.2012.02.026
  • Peer Reviewed
• [Journal Article] Derivatives of Dictyostelium differentiation-inducing factors promote mitogen-activated IL-2 production via AP-1 in Jurkat cells (2011)
  • Author(s): Takahashi K, Murakami M, Kikuchi H, Oshima Y, Kubohara Y
  • Journal Title: Life Sci Volume: 88 Pages: 480-485
  • DOI: 10.1016/j.lfs.2011.01.004
  • Peer Reviewed
• [Journal Article] Association between accumulation of visceral fat and the combination of β3 adrenergic receptor Trp64Arg, β2 adrenergic receptor Arg16Gly and uncoupling protein 1 -3826A>G polymorphisms detected by Smart Amplification Process 2 (2011)
  • Author(s): Tsunekawa K, Yanagawa Y, Aoki T, Morimura T, Araki O, Ogiwara T, Kawai Y, Mitani Y, Lezhava A, Yanagawa M, Hayashizaki Y, Murakami M
  • Journal Title: Endocr J Volume: 58 Pages: 1079-1086
  • DOI: 10.1507/endocrj.EJ11-0148
  • Peer Reviewed
• [Presentation] 内分泌代謝疾患の検査結果のみかた (2014)
  • Author(s): 村上正巳
  • Organizer: 第23回臨床内分泌代謝Update
  • Place of Presentation: 名古屋
  • Year and Date: 20140123-25
• [Presentation] 膵β細胞における3 型甲状腺ホルモン脱ヨード酵素の発現とその調節機構 (2013)
  • Author(s): 秋山滋男, 荻原貴之, 青木智之, 荒木修, 村上正巳
  • Organizer: 第56回日本甲状腺学会学術集会
  • Place of Presentation: 和歌山
  • Year and Date: 20131114-16
• [Presentation] 若年者における75g 経口糖負荷試験における血糖およびインスリン分泌に対する検討 (2013)
  • Author(s): 青木智之, 常川勝彦, 森村匡志, 荒木修, 奈良誠人, 荻原貴之, 木村孝穂, 角野博之, 町田哲男, 村上正巳
  • Organizer: 第60回日本臨床検査医学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 20131031-1103
• [Presentation] Dipeptityl peptidase-4 inhibitors improve glycaemic control in latent autoimmune diabetes in sdults (LADA) patients insufficiently controlled despite insulin therapy (2013)
  • Author(s): Araki O, Nakahara R, Ujiie K, Tsunekawa K, Aoki T, Morimura T, Kimura T, Nara M, Sumino H, Ogiwara T, Murakami M
  • Organizer: 第49回欧州糖尿病学会
  • Place of Presentation: バルセロナ
  • Year and Date: 20130923-27
• [Presentation] インスリン療法中の糖尿病患者に対するシタグリプチン併用の有効性に関するCGM と1, 5-AG による検討 (2013)
  • Author(s): 荒木修, 氏家紘平, 高山真祐子, 中原理恵子, 常川勝彦, 青木智之, 森村匡志, 木村孝穂, 奈良誠人, 角野博之, 荻原貴之, 村上正巳
  • Organizer: 第56回日本糖尿病学会
  • Place of Presentation: 熊本
  • Year and Date: 20130516-18
• [Presentation] バセドウ病の診断と治療 (2012)
  • Author(s): 村上正巳
  • Organizer: 第13回日本内分泌学会関東甲信越支部博術集会
  • Place of Presentation: 宇都宮
  • Year and Date: 20121214-15
• [Presentation] 運動による耐糖能の改善効果に2 型甲状腺ホルモン脱ヨード酵素遺伝子多型が及ぼす影響 (2012)
  • Author(s): 常川勝彦, 青木智之, 森村匡志, 荒木修, 荻原貴之, 川井雄輝, 三谷康正, 林崎良英, 村上正巳
  • Organizer: 第55回日本甲状腺学会
  • Place of Presentation: 福岡
  • Year and Date: 20121129-1201
• [Presentation] 正常ヒト臍帯静脈内皮細胞(HUVEC)における甲状腺ホルモンのnon-genomic effect の検討 (2012)
  • Author(s): 青木智之, 常川勝彦, 森村匡志, 荒木修, 奈良誠人, 荻原貴之, 角野博之, 木村孝穂, 岡島史和, 村上正巳
  • Organizer: 第55回日本甲状腺学会
  • Place of Presentation: 福岡
  • Year and Date: 20121129-1201
• [Presentation] 日本人における2 型甲状腺ホルモン脱ヨード酵素遺伝子多型の糖代謝に及ぼす影響 (2011)
  • Author(s): 常川勝彦, 青木智之, 森村匡志, 荒木修, 荻原貴之, 川井雄輝, 三谷康正, 林崎良英, 村上正巳
  • Organizer: 第54回日本甲状腺学会
  • Place of Presentation: 大阪
  • Year and Date: 20111121-23
• [Presentation] 耐糖能の変化における2 型甲状腺ホルモン脱ヨード酵素遺伝子多型と最大酸素摂取量の関連性の検討 (2011)
  • Author(s): 常川勝彦, 柳川美麿, 青木智之, 森村匡志, 荒木修, 荻原貴之, 古田島伸雄, 四方田幸恵, 三谷康正, 林崎良英, 村上正巳
  • Organizer: 第58回日本臨床検査医学会
  • Place of Presentation: 岡山
  • Year and Date: 20111117-20
• [Book] Nonthyroidal illness(NTI) (2012)
  • Author(s): 村上正巳
  • Total Pages: 2005-2010
  • Publisher: 日本臨床
• [Book] 低T3症候群血中T3濃度が低下するメカニズム (2011)
  • Author(s): 村上正巳
  • Total Pages: 38-41
  • Publisher: 日本甲状腺学会雑誌