Promotion of insulin-induced glucose uptake in C2C12 myotubes by osteocalcin

Shintaro Tsuka, Fumiko Aonuma, Sen Higashi, Tomoko Ohsumi, Koki Nagano, Akiko Mizokami, Tomoyo Kawakubo-Yasukochi, Chihiro Masaki, Ryuji Hosokawa, Masato Hirata, Hiroshi Takeuchi

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)


A close relationship between the bone and systemic glucose metabolism has recently been the center of attention, since the uncarboxylated form of osteocalcin (GluOC), a bone-derived protein, but not the γ-carboxylated form, is involved in glucose metabolism. However, the analysis of GluOC effect using isolated organs and related cell lines are required to understand its roles in a whole systemic metabolic status. In the present study, we examined the effect of GluOC on cell lines derived from skeletal muscle to explore the mechanisms by which GluOC regulates glucose uptake. In the differentiated C2C12 myotubes, GluOC dose-dependently induced the phosphorylation of ERK without affecting intracellular cAMP and Ca2+ levels. This effect was inhibited by U0126, an inhibitor of ERK kinase (MEK). Additionally, U73122, an inhibitor of phospholipase C tended to inhibit it as well. Furthermore, cell treatment with GluOC for a long period promoted insulin-induced Akt phosphorylation and glucose uptake in the myotubes, which was abolished by ERK signaling inhibition. These results indicate that GluOC does not triggered Akt phosphorylation and glucose uptake by itself but promotes insulin-induced glucose uptake in myotubes, probably by up-regulating Akt signaling through ERK activation.

Original languageEnglish
Pages (from-to)437-442
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - Apr 10 2015

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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