Decarboxylated osteocalcin,a possible drug for type 2 diabetes,triggers glucose uptake in MG63 cells  

作　　者：Shi Jin Xiao-Cen Chang Jing Wen Jing Yang Na Ao Ke-Ying Zhang Lin-Na Suo Jian Du 

机构地区：[1]Department of Endocrinology,The Fourth Affiliated Hospital of China Medical University,Shenyang 110032,Liaoning Province,China [2]Department of Endocrinology,The Fifth People’s Hospital of Shenyang,Shenyang 110023,Liaoning Province,China

出　　处：《World Journal of Diabetes》2021年第7期1102-1115,共14页世界糖尿病杂志（英文版）（电子版）

基　　金：Supported by Provincial Science and Technology Department Natural Fund Guidance Project,No.2019-ZD-0774;National Natural Science Foundation of China,No.81470998;Liaoning Ministry of Education,No.LQNK201715;and Liaoning Provincial Doctor Start up Fund,No.20180540008.

摘　　要：BACKGROUND Uncarboxylated osteocalcin(GluOC)has been reported to improve glucose metabolism,prevent type 2 diabetes,and decrease the severity of obesity in mice with type 2 diabetes.GluOC can increase glucose uptake in a variety of cells.Glucose metabolism is the main source of energy for osteoblast proliferation and differentiation.We hypothesized that decarboxylated osteocalcin(dcOC),a kind of GluOC,can increase glucose uptake in MG63 cells(osteoblast-like osteosarcoma cells)and influence their proliferation and differentiation.AIM To investigate the effects of dcOC on glucose uptake in human osteoblast-like osteosarcoma cells and the possible signaling pathways involved.METHODS MG63 cells(human osteoblast-like osteosarcoma cells)were treated with dcOC(0,0.3,3,10,or 30 ng/mL)for 1 and 72 h,and glucose uptake was measured by flow cytometry.The effect of dcOC on cell proliferation was measured with a CCK-8 assay,and alkaline phosphatase(ALP)enzyme activity was measured.PI3K was inhibited with LY294002,and hypoxia-inducible factor 1 alpha(HIF-1α)was silenced with siRNA.Then,GPRC6A(G protein-coupled receptor family C group 6 subtype A),total Akt,phosphorylated Akt,HIF-1α,and glucose transporter 1(GLUT1)levels were measured by Western blot to elucidate the possible pathways by which dcOC modulates glucose uptake.RESULTS The glucose uptake of MG63 cells was significantly increased compared with that of the paired control cells after short-term(1 h)treatment with dcOC at different concentrations(0.3,3,and 10 ng/mL groups,P<0.01;30 ng/mL group,P<0.05).Glucose uptake of MG63 cells was significantly increased compared with that of the paired control cells after long-term(72 h)treatment with dcOC at different concentrations(0.3,3,and 10 ng/mL groups,P<0.01;30 ng/mL group,P<0.05).DcOC triggered Akt phosphorylation in a dose-dependent manner,and the most effective stimulatory concentration of dcOC for short-term(1 h)was 3 ng/mL(P<0.01).LY294002 abolished the dcOC-mediated(1 h)promotion of Akt phosphorylation and glucose u

关 键 词：Decarboxylated osteocalcin OSTEOBLAST Glucose uptake Glucose transporter 1 Type 2 diabetes 

分 类 号：R977.15[医药卫生—药品]