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

• Published in: Biochemical and biophysical research communications 2015-04, Vol.459 (3), p.437-442
• Main Authors: Tsuka, Shintaro, Aonuma, Fumiko, Higashi, Sen, Ohsumi, Tomoko, Nagano, Koki, Mizokami, Akiko, Kawakubo-Yasukochi, Tomoyo, Masaki, Chihiro, Hosokawa, Ryuji, Hirata, Masato, Takeuchi, Hiroshi
• Format: Article
• Language: English
• Subjects: Akt; Animals; Biological Transport, Active - drug effects; Butadienes - pharmacology; Cell Line; Enzyme Inhibitors - pharmacology; ERK; Estrenes - pharmacology; Gene Expression; Glucose - metabolism; Insulin; Insulin - metabolism; MAP Kinase Signaling System - drug effects; Mice; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; Nitriles - pharmacology; Osteocalcin; Osteocalcin - chemistry; Osteocalcin - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Pyrrolidinones - pharmacology; Receptors, G-Protein-Coupled - genetics; Signal Transduction; Skeletal muscle; Type C Phospholipases - antagonists & inhibitors
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.02.123

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. •We examined the direct effect of OC on insulin-induced signaling in the skeletal muscle.•OC promotes insulin-induced Akt phosphorylation and glucose uptake in C2C12 myotubes.•ERK signaling is involved in the effect of OC on insulin-induced Akt signaling.