Hyperglycemia promotes Schwann cell de-differentiation and de-myelination via sorbitol accumulation and Igf1 protein down-regulation

Wu Hao, Syoichi Tashiro, Tomoka Hasegawa, Yuiko Sato, Tami Kobayashi, Toshimi Tando, Eri Katsuyama, Atsuhiro Fujie, Ryuichi Watanabe, Mayu Morita, Kana Miyamoto, Hideo Morioka, Masaya Nakamura, Morio Matsumoto, Norio Amizuka, Yoshiaki Toyama, Takeshi Miyamoto

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28 Citations (Scopus)

Abstract

Diabetes mellitus (DM) is frequently accompanied by complications, such as peripheral nerve neuropathy. Schwann cells play a pivotal role in regulating peripheral nerve function and conduction velocity; however, changes in Schwann cell differentiation status in DM are not fully understood. Here, we report that Schwann cells de-differentiate into immature cells under hyperglycemic conditions as a result of sorbitol accumulation and decreased Igf1 expression in those cells. We found that dedifferentiated Schwann cells could be re-differentiated in vitro into mature cells by treatment with an aldose reductase inhibitor, to reduce sorbitol levels, or with vitaminD<inf>3</inf>, to elevate Igf1 expression. In vivo DM models exhibited significantly reduced nerve function and conduction, Schwann cell de-differentiation, peripheral nerve de-myelination,andall conditionsweresignificantly rescued by aldose reductase inhibitor or vitamin D<inf>3</inf> administration. These findings reveal mechanisms underlying pathological changes in Schwann cells seen in DM and suggest ways to treat neurological conditions associated with this condition.

Original languageEnglish
Pages (from-to)17106-17115
Number of pages10
JournalJournal of Biological Chemistry
Volume290
Issue number28
DOIs
Publication statusPublished - 2015 Jul 10

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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    Hao, W., Tashiro, S., Hasegawa, T., Sato, Y., Kobayashi, T., Tando, T., Katsuyama, E., Fujie, A., Watanabe, R., Morita, M., Miyamoto, K., Morioka, H., Nakamura, M., Matsumoto, M., Amizuka, N., Toyama, Y., & Miyamoto, T. (2015). Hyperglycemia promotes Schwann cell de-differentiation and de-myelination via sorbitol accumulation and Igf1 protein down-regulation. Journal of Biological Chemistry, 290(28), 17106-17115. https://doi.org/10.1074/jbc.M114.631291