[1]金实,赵玉岩,都健.骨钙素及其受体对能量代谢的调节机制[J].国际内分泌代谢杂志,2017,37(06):390-393.
　Jin Shi*,Zhao Yuyan,Du Jian..Regulatory mechanism for energy metabolism by osteocalcin and its receptors[J].International Journal of Endocrinology and Metabolism,2017,37(06):390-393.
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骨钙素及其受体对能量代谢的调节机制()
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《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
37
期数:
2017年06期
页码:
390-393
栏目:
综述
出版日期:
2017-11-20

文章信息/Info

Title:
Regulatory mechanism for energy metabolism by osteocalcin and its receptors
作者:
金实; 赵玉岩; 都健
110032 沈阳,中国医科大学附属第四医院内分泌代谢内科(金实,都健); 110001 沈阳,中国医科大学附属第一医院内分泌代谢内科(赵玉岩)
Author(s):
Jin Shi*;  Zhao Yuyan;  Du Jian.
*Department of Endocrinology and Metabolism, The Fourth Affiliated Hosipital of China Medical University, Shenyang 110032, China
关键词:
骨钙素;  非羧化骨钙素;  GPRC6A;  能量代谢
Keywords:
Osteocalcin;  Uncarboxylated osteocalcin;  GPRC6A;  Energy metabolism
文献标志码:
A
摘要:
骨钙素主要是由成熟的成骨细胞分泌的特异性的非胶原蛋白,可分为羧化骨钙素和非羧化骨钙素。越来越多的研究显示,骨钙素除了可以调节骨基质矿化和骨形成外,还可以增加胰岛素的分泌和胰岛β细胞增殖、减少内脏脂肪、改善胰岛素抵抗,与能量代谢密切相关。G蛋白耦联受体C家族6组成员A(GPRC6A)为骨钙素的受体,参与了相关的机体生理反应。胰岛素信号通路对骨钙素合成起到了调节作用。骨钙素有望成为治疗2型糖尿病、肥胖症等代谢性疾病的新靶点。
Abstract:
Osteocalcin is mainly secreted by mature osteoblasts as specific noncollagenprotein, which can be devided into carboxylated osteocalcin and uncarboxylated osteocalcin. More and more studies show that osteocalcin can improve energy metabolism by enhancing insulin secretion, increasing islet β cell proliferation, reducing visceral adipose tissue, and improving insulin resistance besides regulating bone matrix mineralization and bone formation. As the receptor of osteocalcin, G protein coupled receptor C group 6A takes part in the associated body physiological response. The insulin signaling pathway participates in the regulation of osteocalcin synthesis. Osteocalcin is expected to become a new target for the treatment of type 2 diabetes, obesity and other metabolic diseases.

参考文献/References:

[1] Pi M, Chen L, Huang MZ,et al. GPRC6A null mice exhibit osteopenia, feminization and metabolic syndrome[J].PLoS One,2008,3(12):e3858. DOI:10.1371/journal.pone.0003858.
[2] Pi M, Kapoor K, Ye R, et al. Evidence for osteocalcin binding and activation of GPRC6A in β-cells[J].Endocrinology,2016,157(5):1866-1880. DOI:10.1210/en.2015-2010.
[3] Liu J, Yang J. Uncarboxylated osteocalcin inhibits high glucose-induced ROS production and stimulates osteoblastic differentiation by preventing the activation of PI3K/Akt in MC3T3-E1 cells[J].Int J Mol Med,2016,37(1):173-181. DOI:10.3892/ijmm.2015.2412.
[4] Lee NK, Sowa H, Hinoi E, et al. Endocrine regulation of energy metabolism by the skeleton[J].Cell,2007,130(3):456-469. DOI:10.1016/j.cell.2007.05.047.
[5] Mizokami A, Yasutake Y, Gao J, et al. Osteocalcin induces release of glucagon-like peptide-1 and thereby stimulates insulin secretion in mice[J].PLoS One,2013,8(2):e57375. DOI:10.1371/journal.pone.0057375.
[6] Mizokami A, Yasutake Y, Higashi S, et al. Oral administration of osteocalcin improves glucose utilization by stimulating glucagon-like peptide-1 secretion[J].Bone,2014,69:68-79. DOI:10.1016/j.bone.2014.09.006.
[7] Kawakubo-Yasukochi T, Kondo A, Mizokami A,et al. Maternal oral administration of osteocalcin protects offspring from metabolic impairment in adulthood[J].Obesity(Silver Spring),2016,24(4):895-907. DOI:10.1002/oby.21447.
[8] Wei J, Hanna T, Suda N, et al. Osteocalcin promotes β-cell proliferation during development and adulthood through Gprc6a[J].Diabetes,2014,63(3):1021-1031. DOI:10.2337/db13-0887.
[9] Sabek OM, Nishimoto SK, Fraga D, et al. Osteocalcin effect on human β-cells mass and function[J].Endocrinology,2015,156(9):3137-3146. DOI:10.1210/EN.2015-1143.
[10] Gao J, Bai T, Ren L,et al. The PLC/PKC/Ras/MEK/Kv channel pathway is involved in uncarboxylated osteocalcin-regulated insulin secretion in rats[J].Peptides,2016,86:72-79. DOI:10.1016/j.peptides.2016.10.004.
[11] Kover K, Yan Y, Tong PY,et al. Osteocalcin protects pancreatic beta cell function and survival under high glucose conditions[J].Biochem Biophys Res Commun,2015,462(1):21-26. DOI:10.1016/j.bbrc.2015.04.095.
[12] Tsuka S, Aonuma F, Higashi S, et al. Promotion of insulin-induced glucose uptake in C2C12 myotubes by osteocalcin[J].Biochem Biophys Res Commun,2015,459(3):437-442. DOI:10.1016/j.bbrc.2015.02.123.
[13] Levinger I, Lin X, Zhang X, et al. The effects of muscle contraction and recombinant osteocalcin on insulin sensitivity ex vivo[J].Osteoporos Int,2016,27(2):653-663. DOI:10.1007/s00198-015-3273-0.
[14] Hill HS, Grams J, Walton RG, et al. Carboxylated and uncarboxylated forms of osteocalcin directly modulate the glucose transport system and inflammation in adipocytes[J].Horm Metab Res,2014,46(5):341-347. DOI:10.1055/s-0034-1368709.
[15] Guo Q, Li H, Xu L,et al. Undercarboxylated osteocalcin reverts insulin resistance induced by endoplasmic reticulumstress in human umbilical vein endothelial cells[J].Sci Rep,2017,7(1):46. DOI:10.1038/s41598-017-00163-2.
[16] Chin KY, Ima-Nirwana S, Mohamed IN, et al. Serum osteocalcin is significantly related to indices of obesity and lipid profile in Malaysian men[J].Int J Med Sci,2014,11(2):151-157. DOI:10.7150/ijms.7152.
[17] Redondo MJ, Shirkey BA, Fraga DW, et al. Serum undercarboxylated osteocalcin correlates with hemoglobin A1c in children with recentlydiagnosed pediatric diabetes[J].Pediatr Diabetes,2017,[Epub ahead of print]. DOI:10.1111/pedi.12501.
[18] Sarkar PD, Choudhury AB. Relationships between serum osteocalcin levels versus blood glucose, insulin resistance and markers of systemic inflammation in central Indian type 2 diabetic patients[J].Eur Rev Med Pharmacol Sci,2013,17(12):1631-1635.
[19] Liang Y, Tan A, Liang D, et al. Low osteocalcin level is a risk factor for impaired glucose metabolism in a Chinese male population[J].J Diabetes Investig,2016,7(4):522-528. DOI:10.1111/jdi.12439.
[20] Kim YS, Nam JS, Yeo DW, et al. The effects of aerobic exercise training on serum osteocalcin, adipocytokines and insulin resistance on obese young males[J].Clin Endocrinol(Oxf),2015,82(5):686-694.DOI:10.1111/cen.12601.
[21] Fulzele K, Riddle RC, DiGirolamo DJ, et al. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition[J].Cell,2010,142(2):309-319. DOI:10.1016/j.cell.2010.06.002.
[22] Wei J, Ferron M, Clarke CJ, et al. Bone-specific insulin resistance disrupts whole-body glucose homeostasis via decreased osteocalcin activation[J].J Clin Invest,2014,124(4):1-13. DOI:10.1172/JCI72323.
[23] Vijayan V, Khandelwal M, Manglani K, et al. Homocysteine alters the osteoprotegerin/RANKL system in the osteoblast to promote bone loss: pivotal role of the redox regulator forkhead O1[J].Free Radic Biol Med,2013,61:72-84. DOI:10.1016/j.freeradbiomed.2013.03.004.
[24] Riddle RC, Frey JL, Tomlinson RE, et al. Tsc2 is a molecular checkpoint controlling osteoblast development and glucose homeostasis[J].Mol Cell Biol,2014,34(10):1850-1862. DOI:10.1128/MCB.00075-14.
[25] Abdallah BM, Ditzel N, Laborda J, et al. DLK1 regulates whole-body glucose metabolism: a negative feedback regulation of the osteocalcin-insulin loop[J].Diabetes,2015,64(9):3069-3080. DOI:10.2337/db14-1642.
[26] Bozec A, Bakiri L, Jimenez M,et al. Osteoblast-specific expression of Fra-2/AP-1 controls adiponectin and osteocalcin expression and affects metabolism[J].J Cell Sci,2013,126(Pt 23):5432-5440. DOI:10.1242/jcs.134510.
[27] Ferron M, Lacombe J, Germain A,et al. GGCX and VKORC1 inhibit osteocalcin endocrine functions[J].J Cell Biol,2015,208(6):761-776.DOI:10.1083/jcb.201409111.

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备注/Memo

备注/Memo:
基金项目:辽宁省教育厅项目(L2015567); 辽宁省科技厅公益项目(2014001016)
通信作者:赵玉岩,Email:g572@sina.com; 都健,Email:dujianbox@126.com;
更新日期/Last Update: 2017-11-30