JPWO2011162115A1 - 膵臓β細胞増殖因子を利用した医薬組成物 - Google Patents
膵臓β細胞増殖因子を利用した医薬組成物 Download PDFInfo
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- JPWO2011162115A1 JPWO2011162115A1 JP2012521423A JP2012521423A JPWO2011162115A1 JP WO2011162115 A1 JPWO2011162115 A1 JP WO2011162115A1 JP 2012521423 A JP2012521423 A JP 2012521423A JP 2012521423 A JP2012521423 A JP 2012521423A JP WO2011162115 A1 JPWO2011162115 A1 JP WO2011162115A1
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Abstract
Description
(1)UGGT1遺伝子を発現するベクターを含有することを特徴とする医薬組成物。
(2)糖尿病の予防又は治療に用いられることを特徴とする(1)に記載の医薬組成物。
(3)(1)又は(2)に記載の医薬組成物を非ヒト動物に投与し、その非ヒト動物の膵臓β細胞を増殖させる方法。
(4)UGGT1遺伝子が導入され、この遺伝子が発現していることを特徴とするトランスジェニック非ヒト動物。
(5)UGGT1遺伝子のプロモーターの下流にレポーター遺伝子を連結したベクターで形質転換された細胞。
(6)細胞が、膵臓β細胞であることを特徴とする(5)に記載の細胞。
(7)被験物質の存在下で(5)又は(6)に記載の細胞を培養する工程、及びレポーター遺伝子の発現量を増大させた被験物質を選択する工程を含むことを特徴とする糖尿病の予防薬又は治療薬のスクリーニング方法。
(8)被験物質をUGGT1と共存させ、UGGT1と相互作用をする被験物質を選択する工程、及び前記で選択された被験物質を非ヒト動物に投与し、その非ヒト動物の膵臓β細胞を増殖させる被験物質を選択する工程を含むことを特徴とする糖尿病の予防薬又は治療薬のスクリーニング方法。
ラットインスリンIIプロモーター遺伝子(GeneBankに登録されているRATINSIIに記してある配列の243から1125)にUGGT1遺伝子を組み込んだ発現ベクターを構築し、C3Hマウス及びC57Black6マウスの受精卵に注入し、仮親マウスに同受精卵を入れた。F0マウス出生後、遺伝子型をPCRプライマー199M(5’-GCTCTGACTGACCGCGTTACTCC-3’: 配列番号1)及び201M(5’-GGGAGTGTCCCAGGAATCAGG-3’: 配列番号2)にて確認し、C57Black6マウスへ6回交配させた。そのF6マウス(6ヶ月齢)のUGGT1遺伝子の発現をRT-PCRにより解析した。その結果、導入したUGGT1遺伝子はRNAレベルで膵臓に特異的に発現していた(図1)。
図2及び図3に示すように、UGGT1マウスでは、膵臓ランゲルハンス島の細胞数が顕著に増加していた。そこで、UGGT1マウスにストレプトゾトシンを投与し、糖尿病を誘発させて、UGGT1の治療効果の解析を試みた。ストレプトゾトシンは、膵臓β細胞を特異的に殺し、インスリン濃度を下げて、糖尿病を誘発させる試薬である。投与前に採血し(D0)、投与後48時間後さらに採血し(D2)、その血糖値、インスリン濃度の検定を行った。
引用文献1:Maurizio Molinari, Camela Galli, Omar Vanoni, Stacey M Arnold, Randal J Kaufman.
Persistent glycoprotein misfolding activities the glucosidase II/UGT1-driveb Calnexin cycle to delay aggregation and loss of folding competence.
Molecular Cell vol20, p503-512, 2005
引用文献2:Rui Takahashi, Hisanitsu Ishuhara, KazumaTakahashi, Akira Tamura, Suguru Yamaguchi, Takahiro Yamada, Hideki Katagiri, Yoshitomo Oka.
Efficient and controlled gene expression in mouse pancreatic isltes by arterial delivery of tetracycline-inducible adenoviral vectors.
Journal of Molecular Endocrinology 38:127-136, 2007.
引用文献3:Junta Imai, Hideki Katagiri, Tatsuya Yamada, Yasushi Ishigaki, Takehide Ogihara, Kenji Uno, Yutaka Hasegawa, Junhong Gao, Hisamitsu Ishihara, Hironobu Sasano, Hiroyuki Mizuguchi, Tomoichiro Asano, Yoshitomo Oka.
Constitutively active PDX1 induced efficient insulin production in adult murine liver.
Biochemical and Biophysical Research Communications 326:4022-409, 2005.
引用文献4:Qiao Zhou, Juliana Brown, Andrew Kanarek, Jayaraj Rajagopal, Douglas A Melton.
In vivo reprogramming of adult pancreatic exocrine cells to b-cells.
Nature 455:627-633, 2008.
引用文献5:Doris A Stoffers, Timothty J Kieffer, Mehboob A Hussain, Daniel J Drucker, Susan Bonner-Weir, Joel F Habener, Josephine M Egan.
Insulinotropic Glucagon-like peptide 1 stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas.
Diabetes 49:741-748, 2000.
引用文献6:Junta Imai, Hideki Katagiri, Tetsuya Yamada, Yasushi Ishigaki, Toshinobu Suzuki, Hirohito Kudo, Kenji Uno, Yutaka Hasegawa, Junhong Gao, Keizo Kaneko, Hisamitsu Ishihara, Akira Niijima, Masamitsu Nakazato, Tomoichiro Asano, Yasuhiro Minokoshi, Yoshitomo Oka.
Reluration of pancreatic b cell mass by neuronal signals from the liver.
Science 322:1250-1254, 2008.
引用文献7:Na Kyung Lee, Hideaki Sowa, Eiichi Hinoi, Mathieu Ferron, Jong Deok Ahn,
Cyrille Confavreux, Romain Dacquin, Patrick J Mee, Marc D McKee, Dae Young Jung, Zhiyou Zhang, Jason K Kim, Franck Mauvais-Jarvis, Patricia Ducy, Gerard Karsenty.
Endocrine regulation of energy metabolism by the skeleton.
Cell 130:456-469, 2007.
Claims (8)
- UGGT1遺伝子を発現するベクターを含有することを特徴とする医薬組成物。
- 糖尿病の予防又は治療に用いられることを特徴とする請求項1に記載の医薬組成物。
- 請求項1又は2に記載の医薬組成物を非ヒト動物に投与し、その非ヒト動物の膵臓β細胞を増殖させる方法。
- UGGT1遺伝子が導入され、この遺伝子が発現していることを特徴とするトランスジェニック非ヒト動物。
- UGGT1遺伝子のプロモーターの下流にレポーター遺伝子を連結したベクターで形質転換された細胞。
- 細胞が、膵臓β細胞であることを特徴とする請求項5に記載の細胞。
- 被験物質の存在下で請求項5又は6に記載の細胞を培養する工程、及びレポーター遺伝子の発現量を増大させた被験物質を選択する工程を含むことを特徴とする糖尿病の予防薬又は治療薬のスクリーニング方法。
- 被験物質をUGGT1と共存させ、UGGT1と相互作用をする被験物質を選択する工程、及び前記で選択された被験物質を非ヒト動物に投与し、その非ヒト動物の膵臓β細胞を増殖させる被験物質を選択する工程を含むことを特徴とする糖尿病の予防薬又は治療薬のスクリーニング方法。
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PCT/JP2011/063459 WO2011162115A1 (ja) | 2010-06-21 | 2011-06-13 | 膵臓β細胞増殖因子を利用した医薬組成物 |
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2000515376A (ja) * | 1996-07-19 | 2000-11-21 | ニュー イングランド メディカル センター ホスピタル インク. | 血管保護剤の同定方法 |
JP2003517819A (ja) * | 1999-08-18 | 2003-06-03 | ナショナル・リサーチ・カウンシル・オブ・カナダ | Udp−グルコース:糖タンパク質グルコシルトランスフェラーゼ(uggt)活性のスクリーニング |
JP2006158244A (ja) * | 2004-12-03 | 2006-06-22 | Toray Ind Inc | 新規蛋白質、その医薬用途、その蛋白質の遺伝子のプロモーターおよびその用途 |
WO2010050584A1 (ja) * | 2008-10-31 | 2010-05-06 | 独立行政法人科学技術振興機構 | ヘルパーt細胞の選択的機能制御法 |
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WO2003087768A2 (en) * | 2002-04-12 | 2003-10-23 | Mitokor | Targets for therapeutic intervention identified in the mitochondrial proteome |
JP5137805B2 (ja) | 2008-12-15 | 2013-02-06 | キヤノン株式会社 | 検査システム及びその制御方法、コンピュータプログラム |
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2011
- 2011-06-13 WO PCT/JP2011/063459 patent/WO2011162115A1/ja active Application Filing
- 2011-06-13 JP JP2012521423A patent/JPWO2011162115A1/ja not_active Ceased
- 2011-06-13 EP EP11798001.1A patent/EP2583693A4/en not_active Withdrawn
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000515376A (ja) * | 1996-07-19 | 2000-11-21 | ニュー イングランド メディカル センター ホスピタル インク. | 血管保護剤の同定方法 |
JP2003517819A (ja) * | 1999-08-18 | 2003-06-03 | ナショナル・リサーチ・カウンシル・オブ・カナダ | Udp−グルコース:糖タンパク質グルコシルトランスフェラーゼ(uggt)活性のスクリーニング |
JP2006158244A (ja) * | 2004-12-03 | 2006-06-22 | Toray Ind Inc | 新規蛋白質、その医薬用途、その蛋白質の遺伝子のプロモーターおよびその用途 |
WO2010050584A1 (ja) * | 2008-10-31 | 2010-05-06 | 独立行政法人科学技術振興機構 | ヘルパーt細胞の選択的機能制御法 |
Non-Patent Citations (2)
Title |
---|
JPN6015019401; J. Cell Biol. Vol.189,No.5, 20100531, P.829-841 * |
JPN7015001300; J. Biochem. Vol.120,No.2, 199608, P.236-241 * |
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WO2011162115A1 (ja) | 2011-12-29 |
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