Effect of everolimus on the glucose metabolic pathway in mouse skeletal muscle cells (C2C12)

Kayoko Yoshida, Chiyo K. Imamura, Kanako Hara, Mayumi Mochizuki, Yusuke Tanigawara

研究成果: Article査読

10 被引用数 (Scopus)

抄録

Introduction: Everolimus selectively inhibits mammalian target of rapamycin complex 1 (mTORC1) and exerts an antineoplastic effect. Metabolic disturbance has emerged as a common and unique side effect of everolimus. Objectives: We used targeted metabolomic analysis to investigate the effects of everolimus on the intracellular glycometabolic pathway. Methods: Mouse skeletal muscle cells (C2C12) were exposed to everolimus for 48 h, and changes in intracellular metabolites were determined by capillary electrophoresis time-of-flight mass spectrometry. mRNA abundance, protein expression and activity were measured for enzymes involved in glycometabolism and related pathways. Results: Both extracellular and intracellular glucose levels increased with exposure to everolimus. Most intracellular glycometabolites were decreased by everolimus, including those involved in glycolysis and the pentose phosphate pathway, whereas no changes were observed in the tricarboxylic acid cycle. Everolimus suppressed mRNA expression of enzymes related to glycolysis, downstream of mTOR signaling enzymes and adenosine 5′-monophosphate protein kinases. The activity of key enzymes involved in glycolysis and the pentose phosphate pathway were decreased by everolimus. These results show that everolimus impairs glucose utilization in intracellular metabolism. Conclusions: The present metabolomic analysis indicates that everolimus impairs glucose metabolism in muscle cells by lowering the activities of glycolysis and the pentose phosphate pathway.

本文言語English
論文番号98
ジャーナルMetabolomics
13
8
DOI
出版ステータスPublished - 2017 8月 1

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 臨床生化学

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