Promotion of insulin-induced glucose uptake in C2C12 myotubes by osteocalcin.
Promotion of insulin-induced glucose uptake in C2C12 myotubes by osteocalcin.
复制标题
骨钙素促进 C2C12 肌管中胰岛素诱导的葡萄糖摄取。
DOI：
10.1016/j.bbrc.2015.02.123
复制
发表时间：
2015
影响因子：
3.1
通讯作者：
H.
中科院分区：
文献类型：
--
作者：
Tsuka;S.;Aonuma;F.;Higashi;S.;Ohsumi;T.;Nagano;K.;Mizokami;A.;Kawakubo-Yasukochi;T.;Masaki;C.;Hosokawa;R. and Hirata;M. and Takeuchi;H.
骨与全身葡萄糖代谢之间的密切关系最近已成为关注的中心，因为骨钙素（GluOC）的非羧基化形式（而非γ-羧基化形式）（骨源性蛋白）参与葡萄糖代谢。然而，需要使用离体器官和相关细胞系分析GluOC效应，以了解其在整个系统代谢状态中的作用。在本研究中，我们研究了GluOC对骨骼肌细胞系的影响，以探讨GluOC调节葡萄糖摄取的机制。在分化的C2 C12肌管中，GluOC剂量依赖性地诱导ERK磷酸化，而不影响细胞内cAMP和Ca 2+水平。ERK激酶（MEK）抑制剂U 0126可抑制这种作用。此外，磷脂酶C抑制剂U 73122也有抑制磷脂酶C活性的趋势。此外，细胞处理与GluOC长时间促进胰岛素诱导的Akt磷酸化和葡萄糖摄取的肌管，这是废除ERK信号抑制。这些结果表明，GluOC本身不触发Akt磷酸化和葡萄糖摄取，但促进胰岛素诱导的肌管葡萄糖摄取，可能是通过ERK激活上调Akt信号传导。
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.