Translational control of glucose-induced insulin biosynthesis

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659161
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Nara Medical University
• Principal Investigator: TAKASAWA Shin 奈良県立医科大学, 医学部, 教授 (50187944)
• Co-Investigator(Kenkyū-buntansha): HIRONAKA Asako 奈良県立医科大学, 医学部, 講師 (80211514) ; TSUCHIDA Sumiyo 奈良県立医科大学, 医学部, 教務職員 (70458016)
• Project Period (FY): 2011 – 2012
• Keywords: インスリン / 翻訳調節 / 糖尿病

Research Abstract

Glucose-induced insulin synthesis is important for homeostasis of blood glucose level and regulated by transcription, translation, and secretion. In the present study, we fused several lengths of 5’-untranslated region of human insulin mRNA with protein-destabilization sequence (PEST sequence). We then introduced the fused genes into glucose-sensitive human insulin producing cells (1.1B4 cells) and determined mRNA sequence essential for glucose-induced pro-insulin synthesis by translation. The sequence “GUCCUUCUG” in the 5’-untranslated region of human insulin mRNA was indicated as a sequence essential for translational control of glucose-induced pro-insulin synthesis. The human (Homo sapiens sapiens) sequence was highly conserved in chimpanzee (Pan troglodytes), rat (Rattus norvegicus), mouse (Mus musculus), guinea pig (Cavia Porcellus), pig (Sus scrofa domesticus), bovine(Bos taurus), chicken (Gallus gallus domesticus), leopard frog (Rena pipiens), and zebrafish (Danio rerio) insulin mRNAs; The sequence “NYNSYYNR “ was suggested as consensus sequence for glucose-induced translational control of insulin biosynthesis.

Research Products

• [Journal Article] Prevention of Reg protein-induced β-cell apoptosis by induction of HGF gene transcription (2013)
  • Author(s): Nakagawa, K., Takasawa, S., Nata, K., Yamauchi, A., Itaya-Hironaka, A., Ota, H., Yoshimoto, K., Sakuramoto-Tsuchida, S., Miyaoka, T., Unno, M. and Okamoto, H
  • Journal Title: FEBS Lett
  • Peer Reviewed
• [Journal Article] Expression of REG III and prognosis in head and neck cancer (2013)
  • Author(s): Masui, T., Ota, I., Itaya-Hironaka, A., Takeda, M., Kasai, T., Yamauchi, A., Sakurakoto-Tsuchida, S., Mikami, S., Yane, K., Takasawa, S. and Hosoi, H
  • Journal Title: Oncol. Rep.
  • Peer Reviewed
• [Journal Article] Involvement of autoimmunity to REG, a regeneration factor, in patients with primary Sjogren's syndrome (2013)
  • Author(s): Yoshimoto, K., Fujimoto, T., Itaya-Hironaka, A., Miyaoka, T., Sakuramoto-Tsuchida, S., Yamauchi, A., Fujimura, T., Takeda, M., Kasai, T., Nakagawara, K., Nonomura, A. and Takasawa, S.
  • Journal Title: Clin. Exp. Immunol.
  • Peer Reviewed
• [Journal Article] Reg 3γ gene expression in regenerating skeletal muscle and corresponding nerve (2013)
  • Author(s): Klasan, G.S., Ivanac, D., Erzen, D.J., Picard, A., Takasawa, S., Peharec, S., Arbanas, J., Girotto, D. and Jerkovic, R
  • Journal Title: Muscle Nerve
  • Peer Reviewed
• [Journal Article] The advantages of three-dimensional culture in a collagen hydrogel for stem cell differentiation (2013)
  • Author(s): Naito, H., Yoshimura, M., Takasawa, S., Tojo, T. and Taniguchi, S
  • Journal Title: J.Biomed. Mater. Res. A
  • Peer Reviewed
• [Journal Article] E. Biomarkers for diagnosis and monitoring of Celiac disease (2013)
  • Author(s): Vives-Pi, M., Takasawa, S., Pujol-Autonell, I., Planas, R., Cabre, E., Ojanguren, I., Montraveta, M. Santos, A. L. and Ruiz-Oritz
  • Journal Title: J. Clin. Gastroenterol Volume: vol. 47 Pages: 308-313
  • Peer Reviewed
• [Journal Article] Identification of a major enzyme for the synthesis and hydrolysis of cyclic ADP-ribose in amphibian cells and evolutional conservation of the enzyme from human to invertebrate (2012)
  • Author(s): Ikeda, T., Takasawa, S., Noguchi, N., Nata, K., Yamauchi, A., Takahashi, I., Yoshikawa, T., Sugawara, A., Yonekura, H. and Okamoto,H.
  • Journal Title: Mol. Cell. Biochem Volume: vol. 366 Pages: 69-80
  • Peer Reviewed
• [Journal Article] Attenuation of glucose-induced insulin secretion by intermittent hypoxia via down-regulation of CD38 (2012)
  • Author(s): Ota, H., Tamaki, S., Itaya-Hironaka, A., Yamauchi, A., Sakuramoto-Tsuchida, S., Morioka, T., Takasawa, S. and Kimura, H
  • Journal Title: Life Sci Volume: vol. 90 Pages: 206-211
  • Peer Reviewed
• [Journal Article] Septic shock is associated with receptor for advanced glycation endproducts (RAGE) ligation of LPS (2011)
  • Author(s): Yamamoto, Y., Harashima, A., Saito, H., Tsuneyama, K., Munesue, S., Motoyoshi, S., Han, D., Watanabe, T., Asano, M., Takasawa, S., Okamoto, H., Shimura, S., Karasawa, T., Yonekura, H. and Yamamoto, H
  • Journal Title: J. Immunol Volume: vol. 186 Pages: 3248-3257
  • Peer Reviewed
• [Journal Article] Expression profiling of the REG gene family in colorectal carcinoma (2011)
  • Author(s): Zheng, H.C., Sugawara, A., Okamoto, H., Takasawa, S., Takahashi, H., Masuda, S. and Takano, Y
  • Journal Title: J. Histochem. Cytochem Volume: vol. 59 Pages: 106-115
  • Peer Reviewed
• [Journal Article] Deletion of platelet-derived growth factor-β receptor improves diabetic nephropathy in Ca2+/calmodulin-dependent protein kinase IIα(Thr286Asp) transgenic mice (2011)
  • Author(s): Suzuki, H., Usui, I., Kato, I., Oya, T., Kanatani, Y., Yamazaki, Y., Fujisaka, S., Senda, S., Ishii, Y., Urakaze, M., Mahmood, A., Takasawa, S., Okamoto, H., Kobayashi, M., Tobe, K. and Sasahara, M
  • Journal Title: Diabetologia Volume: vol. 54 Pages: 2953-2962
  • Peer Reviewed
• [Journal Article] The effect of mesenchymal stem cell osteoblastic differentiation on the mechanical properties of engineered bone-like tissue (2011)
  • Author(s): Naito, H., Dohi, Y. Zimmermann, W.-H., Tojo, T., Takasawa, S., Eschenhagen, T. and Taniguchi, S
  • Journal Title: Tissue Engineering Volume: vol. 17 Pages: 2321-2329
  • Peer Reviewed
• [Presentation] Up-regulation of VEGF mRNA by advanced glycation endproducts in hydroquinone-treated human retinal pigment epithelial cells (2013)
  • Author(s): Tsujunaka, H., Itaya-Hironaka, A., Yamauchi, A., Sakuramoto-Tsuchida, S., Ota, H., Fujimura, T., Nochioka, K., Shimoyama, K., Ogata, N. and Takasawa, S
  • Organizer: The 73rd American Diabetes Association Scientific Sessions
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 20130621-25
• [Presentation] Induction of REG Iα, a new auto-antigen in Sjogren's syndrome patients, in salivary duct epithelial cells by interleukin-6 and -11 (2013)
  • Author(s): Fujimura, T., Fujimoto, T, Itaya-Hironaka, A., Miyaoka, T., Yoshimoto, K., Sakuramoto-Tsuchida, S., Yamauchi, A., Tsujinaka, H., Tanaka, Y. and Takasawa, S.
  • Organizer: Annual European Congress of Rheumatology EULAR 2013
  • Place of Presentation: Madrid, Spain
  • Year and Date: 20130612-15
• [Presentation] 加齢黄斑変性症の病型決定に最終糖化産物(AGE)が関与する可能性 (2013)
  • Author(s): 辻中大生、広中安佐子、山内晶世、藤村貴則、土田澄代、後岡克典、下山季美恵、緒方奈保子、高沢 伸
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本市
  • Year and Date: 20130516-18
• [Presentation] 最終糖化産物(AGE)が加齢黄斑変性(AMD)の病型決定因子となる可能性について (2013)
  • Author(s): 辻中大生、後岡克典、下山季美恵、広中安佐子、藤村貴則、山内晶世、高沢 伸、緒方奈保子
  • Organizer: 第117回日本眼科学会総会
  • Place of Presentation: 東京
  • Year and Date: 20130404-07
• [Presentation] 間歇的低酸素による血管平滑筋細胞の増殖促進作用 (2013)
  • Author(s): 京谷陽司、太田浩世、超 晶、長山功佑、伊藤都祐、小澤健太郎、宇野雅之、木村弘、高沢 伸、吉栖 正典
  • Organizer: 第42回日本心脈管作動物質学会
  • Place of Presentation: 奈良市
  • Year and Date: 20130208-09
• [Presentation] 膵β細胞におけるヒト REG (Regenerating gene)ファミリー遺伝子の IL-6/デキサメサゾンによる転写誘導とその機構 (2012)
  • Author(s): 山内晶世、広中安佐子、土田澄代、吉本清巳、宮岡朋子、藤村貴則、辻中大生、土田親次、太田浩世、高沢 伸
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡市
  • Year and Date: 20121214-16
• [Presentation] Intermittent hypoxia stimulates βcell proliferation via up-regulation of Regfamily genes (2012)
  • Author(s): Takasawa, S., Ota, H., Itaya-Hironaka, A., Yamauchi, A., Sakuramoto-Tsuchida, S., Miyaoka, T., Fujimura, T., Tsujinaka, H., Yoshimoto, K., Tsuchida, C., Tamaki, S. and Kimura, H
  • Organizer: The 9thIDF-WPR Congress/4thAASD Scientific Meeting
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20121124-27
• [Presentation] The JAK/STAT signaling is essential for human REG Iα transcription in pancreatic β cells (2012)
  • Author(s): Yamauchi, A., Itaya-Hironaka, A., Sakuramoto-Tsuchida, S., Yoshimoto, K., Miyaoka, T., Fujimura, T., Tsujinaka, H., Tsuchida, C., Ota, H., Takasawa, S
  • Organizer: The 9thIDF-WPR Congress/4thAASD Scientific Meeting
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20121124-27
• [Presentation] 仁骨髄由来間葉系細胞搭載人工骨の骨形成能に対するポリ ADP リボースポリメラーゼ阻害剤の影響 (2012)
  • Author(s): 藤間保晶、土肥祥子、谷掛洋平、高澤 伸、大串 始、赤羽 学、田中康
  • Organizer: 第27回日本整形外科学会基礎学術集会
  • Place of Presentation: 名古屋市
  • Year and Date: 20121026-27
• [Presentation] Fibronectin をコートした βTCP の骨形成能 (2012)
  • Author(s): 谷掛洋平、中島弘司、林 宏治、加藤宣伸、藤間保晶、大串 始、土肥祥子、赤羽 学、高澤 伸、川手健次、田中康仁
  • Organizer: 第27回日本整形外科学会基礎学術集会
  • Place of Presentation: 名古屋市
  • Year and Date: 20121026-27
• [Presentation] 下咽頭癌における REG 遺伝子ファミリーの発現と予後 (2012)
  • Author(s): 桝井貴史、太田一郎、広中安佐子、武田麻衣子、笠井孝彦、細井祐司、高沢 伸
  • Organizer: 第50回日本癌治療学会学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 20121025-27
• [Presentation] Vascular smooth muscle cell proliferation by intermittent hypoxia is independent on the glucose-induced insulin secretion (2012)
  • Author(s): Kyotani, Y., Ota, H., Itaya-Hironaka, A., Yamauchi, A., Sakuramoto-Tsuchida, S., Zhao, J., Kimura, H., Uno, M., Takasawa, S.and Yoshizumi, M
  • Organizer: The 72nd American Diabetes Association Scientific Sessions
  • Place of Presentation: Philadelphia, PA, USA
  • Year and Date: 20120608-12
• [Presentation] 下咽頭癌における REG 遺伝子ファミリーの発現と予後 (2012)
  • Author(s): 桝井貴史、太田一郎、広中安佐子、武田麻衣子、笠井孝彦、細井祐司、高沢 伸
  • Organizer: 第36回日本頭頸部癌学会
  • Place of Presentation: 松江市
  • Year and Date: 20120607-08
• [Presentation] 間歇的低酸素被爆は膵 β 細胞増殖を引き起こす (2012)
  • Author(s): 太田浩世、高沢 伸、玉置伸二、広中安佐子、山内晶世、土田澄代、辻中大生、藤村貴則、宮岡朋子、木村 弘
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 20120517-19
• [Presentation] 睡眠呼吸障害 睡眠時無呼吸症候群に伴う間歇的低酸素曝露によるインスリン分泌障害 (2012)
  • Author(s): 太田浩世、玉置伸二、広中安佐子、山内晶世、土田澄代、山内基雄、吉川雅則、高沢 伸、木村 弘
  • Organizer: 第52回日本呼吸器学会学術講演会
  • Place of Presentation: 神戸市
  • Year and Date: 20120420-22
• [Presentation] Intermittent hypoxia promotes rat vascular muscle cells proliferation with up-regulation of erbB2 receptor and epidermal growth factor family (2012)
  • Author(s): Kyotani, Y., Takasawa, S., Ota, H., Hironaka, A., Yamauchi, A., Tsuchida, S., Zhao, J., Kimura, H., Ito, S. and Yoshizumi, M.
  • Organizer: The 85th Annual Meeting of the Japanese Pharmacological Society
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20120314-16
• [Presentation] CD38 SNP (R140W) is associated with an increased risk of admission to the neonatal intensive care unit (2012)
  • Author(s): Takasawa, S., Enami, N., Itaya-Hironaka, A., Yamauchi, A., Sakuramoto-Tsuchida, S., Miyaoka, T., Yoshimoto, K., Tsujinaka, H., Fujimura, T. and Takahashi, Y
  • Organizer: Asian CD38 and NAD Meeting
  • Place of Presentation: Korea (Invited Lecture)
  • Year and Date: 20120215-18
• [Presentation] Pancreatic β cell proliferation by intermittent hypoxia via up-regulation of Reg family genes (2012)
  • Author(s): Takasawa, S., Ota, H., Itaya-Hironaka, A., Yamauchi, A., Sakuramoto-Tsuchida, S., Miyaoka, T., Fujimura, T., Tsujinaka, H., Yoshimoto, K., Tamaki, S. and Kimura, H
  • Organizer: The 48thEASD Meeting, October 1-5
  • Place of Presentation: Berlin, Germany.
  • Year and Date: 20120000
• [Presentation] 早期肺癌における REG-Iα 遺伝子発現の意義 (2011)
  • Author(s): 木村通孝、内藤 洋、東条 尚、高沢 伸、広中安佐子、土肥祥子、吉村満美子、谷口繁樹
  • Organizer: 第52回日本肺癌学会総会
  • Place of Presentation: 大阪市
  • Year and Date: 20111103-04
• [Presentation] β-TCP に導入した培養骨髄由来細胞の骨形成能の基礎的研究 (2011)
  • Author(s): 谷掛洋平、藤間保晶、土肥祥子、高沢 伸、川手健次、田中康仁
  • Organizer: 第26回日本整形外科学会基礎学術集会
  • Place of Presentation: 前橋市
  • Year and Date: 20111020-21
• [Presentation] 葉系細胞移植後の血管新生・骨形成能に対するポリ ADP リボースポリメラーゼ阻害剤の影響 (2011)
  • Author(s): 藤間保晶、土肥祥子、谷掛洋平、高沢 伸、大串 始、赤羽 学、田中康仁
  • Organizer: 第26回日本整形外科学会基礎学術集会
  • Place of Presentation: 前橋市
  • Year and Date: 20111020-21
• [Presentation] Involvement of autoimmunity to REG in patients with primary Sjogren's syndrome (2011)
  • Author(s): Fujimoto, T., Yoshimoto, K., Itaya-Hironaka, A., Yamauchi, A., Sakuramoto-Tsuchida, S., Miyaoka, T., Takeda, M., Kasai, T., Nonomura, A., Tanaka, Y. and Takasawa, S
  • Organizer: 11thInternational Symposium on Sjogren's syndrome
  • Place of Presentation: Athens, Greece
  • Year and Date: 20110928-1001
• [Presentation] Intermittent hypoxia induces rat smooth muscle cell proliferation with upregulation of erbB2 receptor and epidermal growth factor family mRNAs (2011)
  • Author(s): 京谷陽司、高沢 伸、太田浩世、広中安佐子、山内晶世、土田澄代、木村 弘、宇野雅之、吉栖正典
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都市
  • Year and Date: 20110922-24
• [Presentation] Attenuation of glucose-induced insulin secretion from pancreatic beta cells by intermittent hypoxia via down-regulation of CD38 (2011)
  • Author(s): Ota, H., Tamaki, S., Itaya-Hironaka, A., Yamauchi, A., Sakuramoto-Tsuchida, S., Morioka, T., Takasawa, S. and Kimura, H
  • Organizer: 47thEASD Meeting
  • Place of Presentation: Lisbon, Portugal
  • Year and Date: 20110912-16
• [Presentation] シェーグレン症候群の唾液腺障害におけるREG の関与について (2011)
  • Author(s): 吉本清巳、藤本 隆、広中安佐子、土田澄代、山内晶世、宮岡朋子、武田麻衣子、笠井孝彦、野々村昭孝、高沢 伸
  • Organizer: 第55回日本リュウマチ学会総会・学術集会/第20回国際リウマチシンポジウム
  • Place of Presentation: 神戸市
  • Year and Date: 20110717-20
• [Presentation] REG family genes expression in lung cancer (2011)
  • Author(s): Naito, H., Tojo, T., Kimura, M., Kawaguchi, T., Takasawa, S., Itaya-Hironaka, A., Dohi, Y. and Taniguchi, S
  • Organizer: International Association for the Study of Lung Cancer 2011
  • Place of Presentation: Amsterdam,Netherlands
  • Year and Date: 20110703-07
• [Presentation] Attenuation of glucose-induced insulin secretion by intermittent hypoxia via down-regulation of CD38 (2011)
  • Author(s): Ota, H., Tamaki, S., Itaya-Hironak, A., Yamauchi, A., Sakuramoto-Tsuchida, S., Takasawa, S. and Kimura, H
  • Organizer: The 71stAmerican Diabetes Association Scientific Sessions
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 20110624-28
• [Presentation] IL-6/Dexamethasone activated the human REG Iα gene transcription in pancreatic β-cells via the JAK/STAT signaling pathway (2011)
  • Author(s): Yamauchi, A., Itaya-Hironak, A., Sakuramoto-Tsuchida, S., Yoshimoto, K., Miyaoka, T., Ota, H., Naito, H. and Takasawa, S
  • Organizer: The 71stAmerican Diabetes Association Scientific Sessions
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 20110624-28
• [Presentation] 下咽頭癌における REG 遺伝子ファミリーの発現と予後 (2011)
  • Author(s): 桝井貴史、太田一郎、広中安佐子、武田麻衣子、笠井孝彦、細井祐司、高沢 伸
  • Organizer: 第35回頭頸部癌学会
  • Place of Presentation: 名古屋市
  • Year and Date: 20110608-10
• [Presentation] Involvement of autoimmunity to REG in patients with primary Sjogren's syndrome (2011)
  • Author(s): Yoshimoto, K., Fujimoto, T., Itaya-Hironaka, A., Yamauchi, A., Sakuramoto-Tsuchida, S., Miyaoka, T., Takeda, M., Kasai, T., Nonomura, A. and Takasawa, S
  • Organizer: Annual European Congress of Rheumatology EULAR 2011
  • Place of Presentation: London, UK
  • Year and Date: 20110525-28
• [Presentation] 炎症性刺激によるヒト REG(Regenerating gene) ファミリー遺伝子の転写誘導 (2011)
  • Author(s): 山内晶世、広中安佐子、土田澄代、吉本清巳、宮岡朋子、太田浩世、内藤 洋、高沢 伸
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌市
  • Year and Date: 20110519-21
• [Presentation] 間歇的低酸素被爆によるインスリン分泌障害 (2011)
  • Author(s): 太田浩世、玉置伸二、広中安佐子、山内晶世、土田澄代、高沢 伸、木村 弘
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌市
  • Year and Date: 20110519-21
• [Presentation] 間歇的低酸素被爆による膵β細胞増殖 (2011)
  • Author(s): 高沢 伸、太田浩世、玉置伸二、広中安佐子、山内晶世、土田澄代、木村 弘
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌市
  • Year and Date: 20110519-21
• [Presentation] PDGF-β 受容体の欠損は、インスリン分泌低下型糖尿病モデルマウスの糖尿病腎症を改善する (2011)
  • Author(s): 石井陽子、鈴木ひかり、薄井 勲、加藤一郎、高沢 伸、岡本 宏、小林 正、戸邊一之、笹原正清
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜市
  • Year and Date: 20110428-30
• [Presentation] 睡眠時無呼吸/ガス交換 周期的間歇的低酸素による膵 β 細胞の機能不全と増殖:睡眠時無呼吸症候群と糖尿病との関連の可能性 (2011)
  • Author(s): Ota, H., Tamaki, S., Itaya-Hironaka, A., Yamauchi, A., Sakuramoto-Tsuchida, S., Morioka, T., Takasawa, S. and Kimura, H
  • Organizer: 第51回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 20110422-23
• [Presentation] Dysfunction and proliferation of pancreatic beta-cells by intermittent hypoxia (2011)
  • Author(s): Takasawa, S., Ota, H., Tamaki, S., Itaya-Hironaka, A., Yamauchi, A., Sakuramoto-Tsuchida, S., Yoshimoto, K., Miyaoka, T. and Kimura, H
  • Organizer: Meting for the world-class research hub in East Asia on cADPR and CD38 (Winter conference in Kanazawa 2011)
  • Place of Presentation: Kaga-shi, Japan (Invited Lecture)
  • Year and Date: 20110222-24
• [Presentation] シェーグレン症候群の唾液腺障害におけるREG の関与について (2011)
  • Author(s): 吉本清巳、藤本 隆、広中安佐子、宮岡朋子、土田澄代、山内晶世、武田麻衣子、笠井孝彦、野々村昭孝、高沢 伸
  • Organizer: 第4回奈良シェーグレン症候群研究会
  • Place of Presentation: ホテル日航奈良
  • Year and Date: 2011-06-25
• [Remarks]
  • URL: http://www.naramed-u.ac.jp/~bioch/
• [Patent(Industrial Property Rights)] 予後予測のための大腸癌組織の検査方法 (2011)
  • Inventor(s): 藤原雅彦、城光寺邦信、加藤基史、島田裕之、岡本 宏、高沢 伸、海野倫明、菅原 明
  • Industrial Property Rights Holder: 江東微生物研究所
  • Industrial Property Number: 特開 2011-0033495
  • Filing Date: 2011-02-17