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Insulin-like growth factor-I is required to maintain muscle volume in adult mice

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Abstract

Insulin-like growth factor-I (IGF-I) is a peptide with diverse functions, among them regulation of embryonic development and bone homeostasis. Serum IGF-I levels decline in the elderly; however, IGF-I function in adults has not been clearly defined. Here, we show that IGF-I is required to maintain muscle mass in adults. We crossed Igf-I flox’d and Mx1 Cre mice to yield Mx1 Cre/Igf-Iflox/flox (IGF-I cKO) mice, and deleted Igf-I in adult mice by polyIpolyC injection. We demonstrate that, although serum IGF-I levels significantly decreased after polyIpolyC injection relative to (Igf-Iflox/flox) controls, serum glucose levels were unchanged. However, muscle mass decreased significantly after IGF-I down-regulation, while bone mass remained the same. In IGF-I cKO muscle, expression of anabolic factors such as Eif4e and p70S6K significantly decreased, while expression of catabolic factors MuRF1 and Atrogin-1 was normal and down-regulated, respectively, suggesting that observed muscle mass reduction was due to perturbed muscle metabolism. Our data demonstrate a specific role for IGF-I in maintaining muscle homeostasis in adults.

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Acknowledgements

T. Miyamoto was supported by a Grant-in-Aid for Scientific Research in Japan and a Grant from the Japan Agency for Medical Research and Development. Y. Sato, A. Kanaji, and K. Miyamoto were supported by a Grant-in-Aid for Scientific Research in Japan. This study was supported in part by a Grant-in-Aid for Scientific Research and a Grant from the Translational Research Network Program.

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Satoshi Nakamura, Yuiko Sato, Tami Kobayashi, Takatsugu Oike, Yosuke Kaneko, Kana Miyamoto, Atsushi Funayama, Akihito Oya, Toru Nishiwaki, Morio Matsumoto, Masaya Nakamura, Arihiko Kanaji & Takeshi Miyamoto

  2. Department of Advanced Therapy for Musculoskeletal Disorders, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Yuiko Sato

  3. Department of Musculoskeletal Reconstruction and Regeneration Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Tami Kobayashi & Takeshi Miyamoto

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  1. Satoshi Nakamura
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  2. Yuiko Sato
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  3. Tami Kobayashi
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Correspondence to Arihiko Kanaji or Takeshi Miyamoto.

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Nakamura, S., Sato, Y., Kobayashi, T. et al. Insulin-like growth factor-I is required to maintain muscle volume in adult mice. J Bone Miner Metab 37, 627–635 (2019). https://doi.org/10.1007/s00774-018-0964-6

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