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

  1. Tomoko Kuwabara1,*,
  2. Mohamedi N. Kagalwala2,
  3. Yasuko Onuma1,
  4. Yuzuru Ito1,
  5. Masaki Warashina1,4,
  6. Kazuyuki Terashima1,
  7. Tsukasa Sanosaka3,
  8. Kinichi Nakashima3,
  9. Fred H. Gage2,
  10. Makoto Asashima1,*

Article first published online: 10 OCT 2011

DOI: 10.1002/emmm.201100177

Issue

EMBO Molecular Medicine

EMBO Molecular Medicine

Volume 3, Issue 12, pages 742–754, December 2011

Additional Information

How to Cite

Kuwabara, T., Kagalwala, M. N., Onuma, Y., Ito, Y., Warashina, M., Terashima, K., Sanosaka, T., Nakashima, K., Gage, F. H. and Asashima, M. (2011), Insulin biosynthesis in neuronal progenitors derived from adult hippocampus and the olfactory bulb. EMBO Mol Med, 3: 742–754. doi: 10.1002/emmm.201100177

Author Information

  1. 1

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

  2. 2

    Laboratory of Genetics, The Salk Institute, La Jolla, CA, USA

  3. 3

    Laboratory of Molecular Neuroscience, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Takayama, Ikoma, Japan

  4. 4

    Present address: Genome Research Laboratories, Wako Pure Chemical Industries, Ltd., Amagasaki, Hyogo, Japan

*Tel: +81-298-61-2534; Fax: +81-298-61-2987

Publication History

  1. Issue published online: 1 DEC 2011
  2. Article first published online: 10 OCT 2011
  3. Manuscript Accepted: 8 AUG 2011
  4. Manuscript Revised: 4 AUG 2011
  5. Manuscript Received: 8 MAR 2011

Funded by

  • AIST

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Keywords:

  • diabetes;
  • hippocampus;
  • insulin;
  • neural stem cell;
  • olfactory bulb

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

View Full Article with Supporting Information (HTML) Get PDF (1244K)