Conophylline and Betacellulin-.DELTA.4: an Effective Combination of Differentiation Factors for Pancreatic .BETA. Cells

  • KITAMURA Ryu-ichi
    Institute for Molecular and Cellular Regulation, Gunma University Third Department of Internal Medicine, National Defense Medical College
  • OGATA Takeki
    Institute for Molecular and Cellular Regulation, Gunma University Third Department of Internal Medicine, National Defense Medical College
  • TANAKA Yuji
    Third Department of Internal Medicine, National Defense Medical College
  • MOTOYOSHI Kazuo
    Third Department of Internal Medicine, National Defense Medical College
  • SENO Masaharu
    Department of Bioscience and Technology, Graduate School of Bioscience and Biotechnology, Okayama University Research Center for Biomedical Engineering, Okayama University
  • TAKEI Izumi
    Clinical Laboratory and Internal Medicine, School of Medicine Keio University
  • UMEZAWA Kazuo
    Department of Applied Chemistry, Faculty of Science and Technology, Keio University
  • KOJIMA Itaru
    Institute for Molecular and Cellular Regulation, Gunma University

抄録

Conophylline and betacellulin-δ4 reproduce differentiation-inducing activity of activin A and betacellulin, respectively. We examined the effect of conophylline and betacellulin-δ4 on β cell differentiation. In AR42J cells, conophylline and betacellulin-δ4 converted them into insulin-producing cells. Cells treated with conophylline and betacellulin-δ4 continued to grow after differentiation. Thus, cell number and insulin content were much greater compared to cells treated with activin A and betacellulin. Furthermore, cells treated with conophylline and betacellulin-δ4 secreted insulin in response to glucose. Likewise, conophylline and betacellulin-δ4 converted pancreatic ductal cells into insulin-producing cells. Insulin content, cell number and glucose-evoked insulin secretion were significantly greater than those in cells treated with activin A and betacellulin. Transplantation of pseudoislets prepared using ductal cells treated with conophylline and betacellulin-δ4 was able to reduce effectively the plasma glucose concentration in streptozotocin-treated nude mice. Conophylline and betacellulin-δ4 are effective in inducing differentiation of β cells from progenitors.<br>

収録刊行物

  • Endocrine Journal

    Endocrine Journal 54 (2), 255-264, 2007

    一般社団法人 日本内分泌学会

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