• Open Access

Insulin biosynthesis in neuronal progenitors derived from adult hippocampus and the olfactory bulb

Authors

  • Tomoko Kuwabara,

    Corresponding author
    1. Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Science City, Japan
    • Tomoko Kuwabara, Tel: +81-298-61-2534; Fax: +81-298-61-2987

      Makoto Asashima, Tel: +81-298-61-2529; Fax:+81-298-61-2987

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  • Mohamedi N. Kagalwala,

    1. Laboratory of Genetics, The Salk Institute, La Jolla, CA, USA
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  • Yasuko Onuma,

    1. Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Science City, Japan
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  • Yuzuru Ito,

    1. Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Science City, Japan
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  • Masaki Warashina,

    1. Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Science City, Japan
    2. Present address: Genome Research Laboratories, Wako Pure Chemical Industries, Ltd., Amagasaki, Hyogo, Japan
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  • Kazuyuki Terashima,

    1. Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Science City, Japan
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  • Tsukasa Sanosaka,

    1. Laboratory of Molecular Neuroscience, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Takayama, Ikoma, Japan
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  • Kinichi Nakashima,

    1. Laboratory of Molecular Neuroscience, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Takayama, Ikoma, Japan
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  • Fred H. Gage,

    1. Laboratory of Genetics, The Salk Institute, La Jolla, CA, USA
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  • Makoto Asashima

    Corresponding author
    1. Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Science City, Japan
    • Tomoko Kuwabara, Tel: +81-298-61-2534; Fax: +81-298-61-2987

      Makoto Asashima, Tel: +81-298-61-2529; Fax:+81-298-61-2987

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Abstract

In the present study, we demonstrated that insulin is produced not only in the mammalian pancreas but also in adult neuronal cells derived from the hippocampus and olfactory bulb (OB). Paracrine Wnt3 plays an essential role in promoting the active expression of insulin in both hippocampal and OB-derived neural stem cells. Our analysis indicated that the balance between Wnt3, which triggers the expression of insulin via NeuroD1, and IGFBP-4, which inhibits the original Wnt3 action, is regulated depending on diabetic (DB) status. We also show that adult neural progenitors derived from DB animals retain the ability to give rise to insulin-producing cells and that grafting neuronal progenitors into the pancreas of DB animals reduces glucose levels. This study provides an example of a simple and direct use of adult stem cells from one organ to another, without introducing additional inductive genes.

See accompanying article http://dx.doi.org/10.1002/emmm.201100178

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