Correlation of insulin resistance and motor function in spinal and bulbar muscular atrophy

Hideaki Nakatsuji, Amane Araki, Atsushi Hashizume, Yasuhiro Hijikata, Shinichiro Yamada, Tomonori Inagaki, Keisuke Suzuki, Haruhiko Banno, Noriaki Suga, Yohei Okada, Manabu Ohyama, Tohru Nakagawa, Ken Kishida, Tohru Funahashi, Iichiro Shimomura, Hideyuki Okano, Masahisa Katsuno, Gen Sobue

研究成果: Article

15 引用 (Scopus)

抜粋

This study aimed to evaluate various metabolic parameters in patients with spinal and bulbar muscular atrophy (SBMA), to investigate the association between those indices and disease severity, and to explore the underlying molecular pathogenesis. We compared the degree of obesity, metabolic parameters, and blood pressure in 55 genetically confirmed SBMA patients against those in 483 age- and sex-matched healthy control. In SBMA patients, we investigated the correlation between these factors and motor functional indices. SBMA patients had lower body mass index, blood glucose, and Hemoglobin A1c, but higher blood pressure, homeostasis model assessment of insulin resistance (HOMA-IR, a marker of insulin resistance), total cholesterol, and adiponectin levels than the control subjects. There were no differences in visceral fat areas, high-density lipoprotein-cholesterol (HDL-C), or triglyceride levels in two groups. Revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) correlated positively with HDL-C, but negatively with HOMA-IR. Through stepwise multiple regression analysis, we identified HOMA-IR as a significant metabolic determinant of ALSFRS-R. In biochemical analysis, we found that decreased expressions of insulin receptors, insulin receptor substrate-1 and insulin receptor-β, in autopsied muscles and fibroblasts of SBMA patients. This study demonstrates that SBMA patients have insulin resistance, which is associated with the disease severity. The expressions of insulin receptors are attenuated in the skeletal muscle of SBMA, providing a possible pathomechanism of metabolic alterations. These findings suggested that insulin resistance is a metabolic index reflecting disease severity and pathogenesis as well as a potential therapeutic target for SBMA.

元の言語English
ページ(範囲)839-847
ページ数9
ジャーナルJournal of Neurology
264
発行部数5
DOI
出版物ステータスPublished - 2017 5 1

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

フィンガープリント Correlation of insulin resistance and motor function in spinal and bulbar muscular atrophy' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用

    Nakatsuji, H., Araki, A., Hashizume, A., Hijikata, Y., Yamada, S., Inagaki, T., Suzuki, K., Banno, H., Suga, N., Okada, Y., Ohyama, M., Nakagawa, T., Kishida, K., Funahashi, T., Shimomura, I., Okano, H., Katsuno, M., & Sobue, G. (2017). Correlation of insulin resistance and motor function in spinal and bulbar muscular atrophy. Journal of Neurology, 264(5), 839-847. https://doi.org/10.1007/s00415-017-8405-3