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Nardilysin Is Required for Maintaining Pancreatic ß-Cell Function.
Nishi, Kiyoto; Sato, Yuichi; Ohno, Mikiko; Hiraoka, Yoshinori; Saijo, Sayaka; Sakamoto, Jiro; Chen, Po-Min; Morita, Yusuke; Matsuda, Shintaro; Iwasaki, Kanako; Sugizaki, Kazu; Harada, Norio; Mukumoto, Yoshiko; Kiyonari, Hiroshi; Furuyama, Kenichiro; Kawaguchi, Yoshiya; Uemoto, Shinji; Kita, Toru; Inagaki, Nobuya; Kimura, Takeshi; Nishi, Eiichiro.
Afiliación
  • Nishi K; Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Sato Y; Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Ohno M; Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Hiraoka Y; Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan Division of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Chuo-ku, Kobe, Japan.
  • Saijo S; Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Sakamoto J; Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Chen PM; Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Morita Y; Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Matsuda S; Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Iwasaki K; Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Sugizaki K; Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Harada N; Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Mukumoto Y; Genetic Engineering Team, RIKEN Center for Life Science Technologies, Chuo-ku, Kobe, Japan.
  • Kiyonari H; Genetic Engineering Team, RIKEN Center for Life Science Technologies, Chuo-ku, Kobe, Japan Animal Resource Development Unit, RIKEN Center for Life Science Technologies, Chuo-ku, Kobe, Japan.
  • Furuyama K; Department of Surgery, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Kawaguchi Y; Department of Surgery, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Uemoto S; Department of Surgery, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Kita T; Kobe City Medical Center General Hospital, Chuo-ku, Kobe, Japan.
  • Inagaki N; Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Kimura T; Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
  • Nishi E; Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan nishi@kuhp.kyoto-u.ac.jp.
Diabetes ; 65(10): 3015-27, 2016 10.
Article en En | MEDLINE | ID: mdl-27385158
Type 2 diabetes (T2D) is associated with pancreatic ß-cell dysfunction, manifested by reduced glucose-stimulated insulin secretion (GSIS). Several transcription factors enriched in ß-cells, such as MafA, control ß-cell function by organizing genes involved in GSIS. Here we demonstrate that nardilysin (N-arginine dibasic convertase; Nrd1 and NRDc) critically regulates ß-cell function through MafA. Nrd1(-/-) mice showed glucose intolerance and severely decreased GSIS. Islets isolated from Nrd1(-/-) mice exhibited reduced insulin content and impaired GSIS in vitro. Moreover, ß-cell-specific NRDc-deficient (Nrd1(delß)) mice showed a diabetic phenotype with markedly reduced GSIS. MafA was specifically downregulated in islets from Nrd1(delß) mice, whereas overexpression of NRDc upregulated MafA and insulin expression in INS832/13 cells. Chromatin immunoprecipitation assay revealed that NRDc is associated with Islet-1 in the enhancer region of MafA, where NRDc controls the recruitment of Islet-1 and MafA transcription. Our findings demonstrate that NRDc controls ß-cell function via regulation of the Islet-1-MafA pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metaloendopeptidasas / Células Secretoras de Insulina / Factores de Transcripción Maf de Gran Tamaño Límite: Animals Idioma: En Revista: Diabetes Año: 2016 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metaloendopeptidasas / Células Secretoras de Insulina / Factores de Transcripción Maf de Gran Tamaño Límite: Animals Idioma: En Revista: Diabetes Año: 2016 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos