[1]董肖肖 许凯月 刘建凤 郑少雄.甲基乙二醛:肥胖及糖尿病人群的治疗新靶点[J].国际内分泌代谢杂志,2019,39(02):101-104.[doi:10.3760/cma.j.issn.1673-4157.2019.02.007]
　Dong Xiaoxiao,Xu Kaiyue,Liu Jianfeng,et al.Methylglyoxal: a new therapeutic target for obesity and diabetes[J].International Journal of Endocrinology and Metabolism,2019,39(02):101-104.[doi:10.3760/cma.j.issn.1673-4157.2019.02.007]
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甲基乙二醛:肥胖及糖尿病人群的治疗新靶点()
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《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
39
期数:
2019年02期
页码:
101-104
栏目:
综述
出版日期:
2019-03-20

文章信息/Info

Title:
Methylglyoxal: a new therapeutic target for obesity and diabetes
作者:
董肖肖1 许凯月1 刘建凤1 郑少雄2
1承德医学院附属沧州市人民医院内分泌代谢科 061000; 2天津医科大学第二医院内分泌科 300211
Author(s):
Dong Xiaoxiao;  Xu Kaiyue;  Liu Jianfeng;  Zheng Shaoxiong
1Department of Endocrinology and Metabolism, Cangzhou People's Hospital, Chengde Medical University, Cangzhou 061000, China; 2Department of Endocrinology, The Second Hospital, Tianjin Medical University, Tianjin 300211, China
关键词:
甲基乙二醛;  二羰基应激;  肥胖;  糖尿病
Keywords:
Methylglyoxal;  Dicarbonyl stress;  Obesity;  Diabetes mellitus
DOI:
10.3760/cma.j.issn.1673-4157.2019.02.007
摘要:
甲基乙二醛(MG)是一种高反应性的二羰基化合物,其主要来源于葡萄糖和果糖代谢,也可以来源于食物,是食品添加剂中的一种重要成分。MG可以使蛋白质和DNA反应生成晚期糖基化终末产物(AGEs),具有细胞毒性。MG通过直接的诱发氧化应激反应,使细胞内活性氧簇增加,导致细胞的代谢紊乱与凋亡。在代谢异常和糖尿病患者的体内,这种不正常的二羰基代谢产物的堆积,会引起DNA和蛋白质重构增多,导致细胞和组织功能的失调以及老化与疾病。代谢受损的肥胖及糖尿病患者体内的MG水平明显升高,是代谢紊乱及血管并发症发生的重要危险信号。乙二醛酶系统代谢可以解毒MG,使其转化成无毒的乳酸盐排出体外,不足以产生毒性反应。提高乙二醛酶1的活性可以降解MG并抑制AGEs的产生,达到解毒的作用。通过解毒MG途径,为糖尿病的诊治提供了一条全新的思路。
Abstract:
Methylglyoxal(MG), a highly reactive dicarbonyl compound, is mainly derived from glucose and fructose metabolism, and can also be derived from food, which is an important ingredient in food additives. MG can make protein and DNA react to form advanced glycosylated end products(AGEs), which is cytotoxic. By directly inducing oxidative stress, MG increases intracellular reactive oxygen species, leading to cell metabolic disorders and apoptosis. In patients with metabolic abnormalities and diabetes, the accumulation of this abnormal dicarbonyl metabolite causes an increase in DNA and protein remodeling, leading to dysfunction of cell and tissue functions, aging and disease. In obese patients with impaired metabolism and diabetic patients, MG level is significantly increased, which is an important risk signal for metabolic disorders and vascular complications. The systematic metabolism of glyoxalase can detoxify MG and make it into non-toxic lactate salt to be expelled from the body, which is not enough to produce toxic reaction. Increasing the activity of glyoxalase 1 can degrade MG and inhibit the production of AGEs to achieve detoxification. Through the way of detoxifying MG, it provides a new idea for the diagnosis and treatment for diabetes.

参考文献/References:

[1] Carracher AM,Marathe PH,Close KL.International Diabetes Federation 2017[J].J Diabetes,2018,10(5):353-356.DOI:10.1111/1753-0407.12644.
[2] Arroyo-Johnson C,Mincey KD.Obesity epidemiology worldwide[J].Gastroenterol Clin North Am,2016,45(4):571-579.DOI:10.1016/j.gtc.2016.07.012.
[3] Nemet I, Varga-Defterdarovi L, Turk Z. Methylglyoxal in food and living organisms[J].Mol Nutr Food Res,2006,50(12):1105-1117.DOI:10.1002/mnfr.200600065.
[4] Degen J,Hellwig M,Henle T.1,2-dicarbonyl compounds in commonly consumed foods[J].J Agric Food Chem,2012,60(28):7071-7079.DOI:10.1021/jf301306g.
[5] Nigro C,Leone A,Raciti GA,et al.Methylglyoxal-Glyoxalase 1 balance: the root of vascular damage[J].Int J Mol Sci,2017,18(1):pii:E188.DOI:10.3390/ijms18010188.
[6] Pastor-Belda M,Fernández-García AJ,Campillo N,et al.Glyoxal and methylglyoxal as urinary markers of diabetes. Determination using a dispersive liquid-liquid microextraction procedure combined with gas chromatography-mass spectrometry[J].J Chromatogr A,2017,1509:43-49.DOI:10.1016/j.chroma.2017.06.041.
[7] Maessen DE,Stehouwer CD,Schalkwijk CG.The role of methylglyoxal and the glyoxalase system in diabetes and other age-relateddiseases[J].Clin Sci(Lond),2015,128(12):839-861.DOI:10.1042/CS20140683.
[8] Rabbani N,Xue M,Thornalley PJ.Activity, regulation, copy number and function in the glyoxalase system[J].Biochem Soc Trans,2014,42(2):419-424.DOI:10.1042/BST20140008.
[9] Thornalley PJ.Glyoxalase I--structure,function and a critical role in the enzymatic defence against glycation[J].Biochem Soc Trans,2003,31(Pt 6):1343-1348.
[10] Xue M,Rabbani N,Thornalley PJ.Glyoxalase in ageing[J].Semin Cell Dev Biol,2011,22(3):293-301.DOI:10.1016/j.semcdb.2011.02.013.
[11] 孔祥,黄凯,张洪梅,等,高效液相色谱-串联质谱法检测糖尿病患者血浆甲基乙二醛和乙二醛浓度[J].上海交通大学学报,2013,33(8):1182-1186. DOI:10.3969/j.issn.1674-8115.2013.08.030.
[12] Xue M, Weickert MO,Qureshi S,et al.Improved glycemic control and vascular function in overweight and obese subjects by glyoxalase 1 inducer formulation[J].Diabetes,2016,65(8):2282-2294.DOI:10.2337/db16-0153.
[13] Adolphe JL,Drew MD,Huang Q,et al.Postprandial impairment of flow-mediated dilation and elevated methylglyoxal after simple but not complex carbohydrate consumption in dogs[J].Nutr Res,2012,32(4):278-284.DOI:10.1016/j.nutres.2012.03.002.
[14] 唐勇军,杜军.糖尿病并发症治疗的新靶点甲基乙二醛[J].中国新药杂志,2006,15(18):1530-1534.DOI:10.3321/j.issn:1003-3734.2006.18.006.
[15] Xue M,Weickert MO,Qureshi S,et al.Improved glycemic control and vascular function in overweight and obese subjects by glyoxalase 1 inducer formulation[J].Diabetes,2016,65(8):2282-2294.DOI:10.2337/db16-0153.
[16] Tezuka Y,Nakaya I,Nakayama K,et al.Methylglyoxal as a prognostic factor in patients with chronic kidney disease[J].Nephrology(Carlton),2018. DOI:10.1111/nep.13526.
[17] Genuth S,Sun W,Cleary P,et al.Skin advanced glycation end products glucosepane and methylglyoxal hydroimidazolone are independently associated with long-term microvascular complication progression of type 1 diabetes[J].Diabetes,2015,64(1):266-278.DOI:10.2337/db14-0215.
[18] Spanos C,Maldonado EM,Fisher CP,et al.Proteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease[J].Proteome Sci,2018,16:4.DOI:10.1186/s12953-018-0131-y.
[19] Moraru A,Wiederstein J,Pfaff D,et al. Elevated levels of the reactive metabolic methylglyoxal recapitulate progression of type 2 diabetes[J]. Cell Metab,2018,27(4):926-934. DOI:10.1016/j.cmet.2018.02.003.
[20] 张秋萍.神经节苷脂联合硫辛酸对糖尿病感觉神经受损患者肢体末端感觉功能及MGO NF-κB的影响[J].中国实用神经疾病杂志,2017,20(12):52-53.DOI:10.3969/j.issn.1673-5110.2017.12.018.
[21] Meeprom A,Chan CB,Sompong W,et al.Isoferulic acid attenuates methylglyoxal-induced apoptosis in INS-1 rat pancreatic β-cell through mitochondrial survival pathways and increasing glyoxalase-1 activity[J].Biomed Pharmacother,2018,101:777-785.DOI:10.1016/j.biopha.2018.01.017.
[22] Hwang SL,Lin JA,Shih PH,et al. Pro-cellular survival and neuroprotection of citrus flavonoid: the actions of hesperetin in PC12 cells[J].Food Funct,2012,3(10):1082-1090.DOI:10.1039/c2fo30100h.

备注/Memo

备注/Memo:
通信作者:刘建凤,Email:liujianfeng5500@163.com
Corresponding author: Liu Jianfeng, Email: liujianfeng5500@163.com
更新日期/Last Update: 2019-03-20