Gas6与2型糖尿病及其并发症的研究进展

董雪娥; 李会芳

Gas6与2型糖尿病及其并发症的研究进展

昆明医科大学第一附属医院糖尿病科

基金项目:

基金：国家自然科学基金资助项目 (81160104, 30760087); 云南省卫生科技计划项目 (2017NS049);

计量
- 文章访问数: 2973
- HTML全文浏览量: 1064
- PDF下载量: 115
- 被引次数: 0
出版历程
- 收稿日期: 2017-08-19

Research Progress of Gas6 with Type 2Diabetes Mellitus and Diabetic Complications

Dong Xue E ,
Li Hui Fang

Funds:

基金：国家自然科学基金资助项目 (81160104, 30760087); 云南省卫生科技计划项目 (2017NS049);

摘要

摘要: 生长停滞特异性蛋白6 (growth arrest-specific 6, Gas6) 是维生素K依赖蛋白家族成员, 属于受体酪氨酸激酶家族TAM (Tyro3, Axl, Mer) 的配体.Gas6/Axl信号途径参与细胞的黏附、迁移、增殖、凋亡、血小板聚集, 血管重塑、炎症及免疫反应等病理生理过程.近年来, 研究发现Gas6/Axl信号通路、Gas6水平及其基因多态性与2型糖尿病、肥胖、胰岛素抵抗和糖尿病并发症显著相关.就Gas6与2型糖尿病及其并发症的相关性作一综述.
- Gas6 /
- 2型糖尿病 /
- 肥胖 /
- 胰岛素抵抗 /
- 并发症
Abstract: Growth arrest-specific 6, which is a member of the vitamin K-dependent protein family, is a ligand of TAM (Tyro3, Axl, Mer) belonging to the receptor tyrosine kinase family.Gas6/Axl signaling pathways are involved in pathophysiological processes of cell adhesion, migration, proliferation, apoptosis, platelet aggregation, vascular remodeling, inflammatory and immune responses. In recent years, studies found that Gas6/Axl signaling pathway, Gas6 level and the gene polymorphism of Gas6 were significantly associated with type 2 diabetes, obesity, insulin resistance and diabetic complications.This article reviews the correlation between Gas6 and type 2 diabetes and its complications
- Growth arrest-specific 6 /
- Type 2 diabetes mellitus /
- Obesity /
- Insulin resistance /
- Diabetic complications

HTML全文

参考文献(49)

[1]	[1]OGURTSOVA K, DA R F J, HUANG Y, et al.IDF Diabetes atlas:Global estimates for the prevalence of diabetes for 2015 and 2040[J].Diabetes Res Clin Pract, 2017, 128:40-50.
[2]	[2]BRAGG F, HOLMES M V, IONA A, et al.Association between diabetes and cause-specific mortality in rural and urban areas of china[J].Jama, 2017, 317 (3) :280-289.
[3]	[3]DIHINGIA A, KALITA J, MANNA P.Implication of a novel Gla-containing protein, Gas6 in the pathogenesis of insulin resistance, impaired glucose homeostasis, and inflammation:A review[J].Diabetes Research&Clinical Practice, 2017, 128:74-82.
[4]	[4]SCHNEIDER C, KING R M, PHILIPSON L.Genes specifically expressed at growth arrest of mammalian cells.[J].Cell, 1988, 54 (6) :787-793.
[5]	[5]MANFIOLETTI G, BRANCOLINI C, AVANZI G, et al.The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade[J].Molecular&Cellular Biology, 1993, 13 (8) :4976-4985.
[6]	[6]LAURANCE S, LEMARI C A, BLOSTEIN M D.Growth arrest-specific gene 6 (gas6) and vascular hemostasis[J].Advances in Nutrition, 2012, 3 (2) :196-203.
[7]	[7]AXELROD H, PIENTA K J.Axl as a mediator of cellular growth and survival[J].Oncotarget, 2014, 5 (19) :8818-8852.
[8]	[8]NAGATA K, OHASHI K, NAKANO T, et al.Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases[J].Journal of Biological Chemistry, 1996, 271 (47) :30022-30027.
[9]	[9]AUGUSTINE K A, ROSSI R M, VAN G, et al.Noninsulin-dependent diabetes mellitus occurs in mice ectopically expressing the human Axl tyrosine kinase receptor[J].Journal of Cellular Physiology, 1999, 181 (3) :433-447.
[10]	[10]SCROYEN I, FREDERIX L, LIJNEN H R.Axl deficiency does not affect adipogenesis or adipose tissue development.[J].Obesity, 2012, 20 (6) :1168-1173.
[11]高娟, 郭萌, 霍学云, 等.GAS6/AXL信号通路失活对小鼠能量代谢的影响[J].中国实验动物学报, 2014, 22 (1) :57-62.
[12]	[12]ASANO T, FUJISHIRO M, KUSHIYAMA A, et al.Role of phosphatidylinositol 3-kinase activation on insulin action and its alteration in diabetic conditions[J].Biological&Pharmaceutical Bulletin, 2007, 30 (9) :1610-1616.
[13]	[13]KHAN K H, WONG M, RIHAWI K, et al.Hyperglycemia and phosphatidylinositol 3-kinase/protein kinase B/Mammalian target of rapamycin (PI3K/AKT/m TOR) inhibitors in phase I trials:Incidence, predictivefactors, and management[J].Oncologist, 2016, 21 (7) :855-860.
[14]	[14]HAN C, MU J, KIM J K, et al.Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKBβ) [J].Science, 2001, 292 (5522) :1728-1731.
[15]高宁.不同糖耐量患者血浆Gas6水平变化及与hsCRP、visfatin和PWV等的关系研究[D].济南:山东大学, 2012.
[16]陈玲.血清生长停滞特异性基因产物6与2型糖尿病的相关性研究[D].苏州:苏州大学, 2013.
[17]	[17]HUNG Y J, LEE C H, CHU N F, et al.Plasma protein growth arrest-specific 6 levels are associated with altered glucose tolerance, inflammation, and endothelial dysfunction[J].Diabetes Care, 2010, 33 (8) :1840-1844.
[18]	[18]LEE C H, CHU N F, SHIEH Y S, et al.The growth arrest-specific 6 (Gas6) gene polymorphism c.834+7G>A is associated with type 2 diabetes.[J].Diabetes Research&Clinical Practice, 2012, 95 (2) :201-206.
[19]	[19]LEE C H, SHIEH Y S, HSIAO F C, et al.High glucose induces human endothelial dysfunction through an Axldependent mechanism[J].Cardiovascular Diabetology, 2014, 13 (1) :1-13.
[20]	[20]HSIEH C H, CHUNG R H, LEE W J, et al.Effect of common gnetic variants of growth arrest-specific 6 gene on insulin resistance, obesity and type 2 diabetes in an asian population[J].Plos One, 2015, 10 (8) :e0135681.
[21]	[21]FOUAD N A, ELTAHER S M, ABDULLAH O A, et al.Serum level of growth arrest-specific 6 (Gas6) protein and genetic variations in the gas6 gene in patients with type 2 diabetes mellitus[J].Egypt J Immunol, 2015, 22 (1) :41-47.
[22]	[22]KAZAKOVA E V, ZGHUANG T, LI T, et al.The Gas6gene rs8191974 and Ap3s2 gene rs2028299 are associated with type 2 diabetes in the northern Chinese Han population[J].Acta Biochimica Polonica, 2017, 64 (2) :227-231.
[23]	[23]Maquoi E, VOROS G, CARMELIET P, et al.Role of gas-6 in adipogenesis and nutritionally induced adipose tissue development in mice[J].Arteriosclerosis Thrombosis&Vascular Biology, 2005, 25 (5) :1002-1007.
[24]	[24]LIJNEN H R, CHRISTIAENS V, SCROYEN L.Growth arrest-specific protein 6 receptor antagonism impairs adipocyte differentiation and adipose tissue development in mice[J].Journal of Pharmacology&Experimental Therapeutics, 2011, 337 (2) :457-464.
[25]	[25]WU K S, HUNG Y J, LEE C H, et al.The involvement of GAS6 signaling in the development of obesity and associated inflammation[J].International Journal of Endocrinology, 2015, 2015:1-7.
[26]	[26]HSIAO F C, LIN Y F, HSIEH P S, et al.Circulating growth arrest-specific 6 protein is associated with adiposity, systemic inflammation, and insulin resistance among overweight and obese adolescents[J].Journal of Clinical Endocrinology&Metabolism, 2013, 98 (2) :E267-E274.
[27]	[27]HSIAO F C, LIN Y F, HSIEH P S, et al.Effect of GAS6and AXL gene polymorphisms on aiposity, systemic inflamma-tion, and insulin resistance in adolescents[J].International Journal of Endocrinology, 2014, 2014 (8) :674069.
[28]	[28]KUO F C, HUNG Y J, SHIEH Y S, et al.The levels of plasma growth arrest-specific protein 6 is associated with insulin sensitivity and inflammation in women[J].Diabetes Res Clin Pract, 2014, 103 (2) :304-309.
[29]	[29]HUNG Y J, LEE C H, SHIEH Y S, et al.Plasma growth arrest-specific protein 6 levels in premenopausal and postmenopausal women:the role of endogenous estrogen[J].Endocrine, 2014, 47 (3) :923-929.
[30]	[30]HUNG Y, LEE C, SHIEH Y, et al.Gender differences in plasma growth arrest-specific protein 6 levels in adult subjects[J].Clinica Chimica Acta, 2015, 441:1-5.
[31]	[31]YANAGITA M, ISHII K, OZAKI H, et al.Mechanism of inhibitory effect of warfarin on mesangial cell proliferation[J].Journal of the American Society of Nephrology Jasn, 1999, 10 (12) :2503-2509.
[32]	[32]YANAGITA M, ARAI H, ISHII K, et al.Gas6 Regulates Mesangial Cell Proliferation through Axl in Experimental Glomerulonephritis[J].American Journal of Pathology, 2001, 158 (4) :1423-1432.
[33]	[33]NAGAI K, ARAI H, YANAGITA M, et al.Growth arrest-specific gene 6 is involved in glomerular hypertrophy in the early stage of diabetic nephropathy[J].Journal of Biological Chemistry, 2003, 278 (20) :18229-18234.
[34]	[34]YANAGITA M.Gas6, warfarin, and kidney diseases[J].Clinical&Experimental Nephrology, 2004, 8 (4) :304-309.
[35]	[35]YANAGITA M.The role of the vitamin K-dependent growth factor Gas6 in glomerular pathophysiology[J].Curr Opin Nephrol Hypertens, 2004, 13 (4) :465-470.
[36]	[36]NAGAI K, MATSUBARA T, MIMA A, et al.Gas6 induces Akt/m TOR-mediated mesangial hypertrophy in diabetic nephropathy[J].Kidney International, 2005, 68 (2) :552-561.
[37]	[37]ARAI H, NAGAI K, DOI T.Role of growth arrest-specific gene 6 in diabetic nephropathy[J].Vitamins&Hormones, 2008, 78:375-392.
[38]	[38]EREK-TOPRAK A, BINGOL-OZAKPINAR O, KARACA Z, et al.Association of plasma growth arrest-specific protein 6 (Gas6) concentrations with albuminuria in patients with type 2 diabetes[J].Renal Failure, 2014, 36 (5) :737-742.
[39]	[39]ERKOC R, CIKRIKCIOGLU MA, AINTAB E, et al.GAS6 intron 8 c.834+7G>A gene polymorphism in diabetic nephropathy[J].Ren Fail, 2015, 37 (5) :866-870.
[40]	[40]LI W, WANG J, GE L, et al.Growth arrest-specific protein 6 (Gas6) as a noninvasive biomarker for early detection of diabetic nephropathy[J].Clin Exp Hypertens, 2017, 39 (4) :382-387.
[41]邱翠婷.维生素K2抑制大鼠血管钙化机制研究[D].西安:第四军医大学, 2015.
[42]姜晓宇.维生素K2逆转华法令诱导大鼠主动脉钙化及其机制研究[D].西安:第四军医大学, 2015.
[43]	[43]QIU C, ZHENG H, TAO H, et al.Vitamin K2 inhibits rat vascular smooth muscle cell calcification by restoring the Gas6/Axl/Akt anti-apoptotic pathway.[J].Molecular&Cellular Biochemistry, 2017, (3) :1-11.
[44]	[44]MUOZ X, SUMOY L, RAM?REZ-LORCA R, et al.Human vitamin K-dependent GAS6:gene structure, allelic variation, and association with stroke[J].Human Mutation, 2004, 23 (5) :506-512.
[45]	[45]MUOZ X, OBACH V, HURTADO B, et al.Association of specific haplotypes of GAS6 gene with stroke.[J].Thromb Haemost, 2007, 98 (2) :406-412.
[46]	[46]JIANG L, LIU C Y, YANG Q F, et al.Plasma level of growth arrest specific 6 (GAS6) protein and genetic variations in the GAS6 gene in patients with acute goronary syndrome[J].American Journal of Clinical Pathology, 2009, 131 (5) :738-743.
[47]姜蕾.GAS6参与动脉粥样硬化发病机制的基础与临床研究[D].武汉:华中科技大学, 2011.
[48]唐开放, 潘学谊, 李铭杰, 等.血浆Gas6水平及其基因多态性与心脑血栓性疾病的相关性研究[J].血栓与止血学, 2012, 18 (1) :9-13.
[49]	[49]CAVET M E, SMOLOCK E M, OZTURK O H, et al.Gas6-axl receptor signaling is regulated by glucose in vascular smooth muscle cells[J].Arteriosclerosis Thrombosis&Vascular Biology, 2008, 28 (5) :886-891.

相关文章(20)

[1]	常宇, 桂莉, 李若楠. 利拉鲁肽改善2型糖尿病胰岛β细胞功能的观察, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20250219
[2]	牛玲, 李博一, 苗翠娟, 张程, 唐艳, 刘方, 马蓉. 瘦素、尿酸与2型糖尿病合并肥胖的关系, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20231121
[3]	李博一, 牛玲, 马蓉, 张娴, 刘方, 唐艳, 苗翠娟, 张程, 韩竺君. 护骨素基因启动子区T950C多态性与2型糖尿病合并骨质疏松症的关系, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20220306
[4]	牛玲, 李博一, 张程, 马蓉, 唐艳, 刘方, 尹利民, 韩竺君, 苗翠娟, 张娴. 降钙素受体、维生素D受体基因多态性与昆明地区2型糖尿病合并骨质疏松的关系, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20211114
[5]	唐嘉黛, 谢琳, 宋红莉, 陈娇娇. 代谢综合征与胃癌发生发展的相关性研究, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20211130
[6]	牛玲, 李博一, 毛静秋, 唐艳, 马蓉, 刘方, 张程, 韩竹君, 苗翠娟, 张娴. 维生素D受体基因多态性与昆明地区2型糖尿病伴骨质疏松症的关系, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20210711
[7]	李博一, 牛玲, 马蓉, 张娴, 刘方, 唐艳, 苗翠娟, 韩竺君, 张程. 护骨素基因启动子区T950C多态性与昆明地区2型糖尿病伴骨质疏松症的关系, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20211112
[8]	杨璐, 施文军, 赵玲, 杜士刚, 陈珮琪, 柯亭羽. 2型糖尿病患者内脏脂肪面积与肥胖及糖脂代谢指标的相关性, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20210932
[9]	乐小婧, 陈婕, 张帆, 李会芳. 代谢综合征与2型糖尿病的相关研究进展, 昆明医科大学学报.
[10]	范译丹, 陈玉, 饶春梅, 高雪娟, 张芳, 方山丹, 向润清, 范源, 吴洋. T2DM患者合并非酒精性脂肪肝与胰岛β细胞功能和胰岛素抵抗的关系, 昆明医科大学学报.
[11]	汪君民, 吴晓虹, 王丽, 雷德鸿, 邱良武. 游泳运动对Fetuin-A诱导的胰岛素抵抗大鼠血清IL-2、IL-6的影响, 昆明医科大学学报.
[12]	李晓红, 马润玫, 陈卓. 肥胖、胰岛素抵抗对妊娠期糖尿病患者血清网膜素-1水平的影响, 昆明医科大学学报.
[13]	李沛. 改良型Clavien手术并发症分级系统分析微通道经皮肾镜取石术后并发症, 昆明医科大学学报.
[14]	蒋婷婷. 脂肪因子Vaspin、Apelin及瘦素与多囊卵巢综合征的相关性, 昆明医科大学学报.
[15]	桂琦. 血清中脂肪因子Apelin、Vaspin、瘦素与子宫内膜癌的相关性, 昆明医科大学学报.
[16]	向茜. 25羟维生素D与2型糖尿病肾病的关系, 昆明医科大学学报.
[17]	杜娟. 大鼠2型糖尿病模型制备方法探讨, 昆明医科大学学报.
[18]	刘淑清. 2型糖尿病胰岛素抵抗与认知功能障碍关系研究, 昆明医科大学学报.
[19]	李显丽. 艾塞那肽治疗肥胖2型糖尿病的临床疗效观察, 昆明医科大学学报.
[20]	桂莉. 2型糖尿病大鼠骨骼肌氧化应激与胰岛素抵抗的关系, 昆明医科大学学报.