支链氨基酸代谢与2型糖尿病的相关性
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摘要
随着科研技术的不断发展和检测手段的不断进步,支链氨基酸(BCAAs)越来越多的被发现在2型糖尿病(T2DM)中发挥着重要的作用,影响着2型糖尿病患者的病情发展。支链氨基酸包括亮氨酸(Leu),异亮氨酸(Ile)和缬氨酸(Val),其代谢过程与2型糖尿病病情发展的相互影响机制尚不明确。这篇综述的目的是介绍支链氨基酸代谢与2型糖尿病的相关性并对国内外现存的各种关于支链氨基酸代谢与2型糖尿病的相互作用可能机制推测的总结,可有助于开发新型有效的2型糖尿病的疗法。
Nowadays,with the continuous development of scientific research technology and the continuous progress of testing methods,Branched chain amino acids( BCAAs) are found to be playing an increasingly important role in type 2 diabetes mellitus( T2 DM),affecting the development of type 2 diabetes. Branched-chain amino acids include leucine,isoleucine and valine,and the mechanism of their influence on the development of type 2 diabetes remains unclear. The purpose of this review is to introduce the correlation between branched-chain amino acid metabolism and type 2 diabetes mellitus,and to provide a summary of the possible mechanisms of the interaction between branch chain amino acid metabolism and type 2 diabetes mellitus at home and abroad. It can help develop new and effective treatments for type 2 diabetes.
Nowadays,with the continuous development of scientific research technology and the continuous progress of testing methods,Branched chain amino acids( BCAAs) are found to be playing an increasingly important role in type 2 diabetes mellitus( T2 DM),affecting the development of type 2 diabetes. Branched-chain amino acids include leucine,isoleucine and valine,and the mechanism of their influence on the development of type 2 diabetes remains unclear. The purpose of this review is to introduce the correlation between branched-chain amino acid metabolism and type 2 diabetes mellitus,and to provide a summary of the possible mechanisms of the interaction between branch chain amino acid metabolism and type 2 diabetes mellitus at home and abroad. It can help develop new and effective treatments for type 2 diabetes.
引文
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[2] Okekunle AP,Li Y,Liu L,et al. Abnormal circulating amino acid profiles in multiple metabolic disorders[J]. Dia-betes Res Clin Pract,2017,132(7):45-58.
[3] Hu W,Sun L,Gong Y,et al. Relationship between branchedchain amino acids,metabolic syndrome,and cardiovascular risk profile in a chinese population:A cross-sectional study[J]. Int J Endocrinol,2016:8173905.
[4] Batch BC,Shah SH,Newgard CB,et al. Branched chain amino acids are novel biomarkers for discrimination of metabolic wellness[J]. Metabolism,2013,62(7):91-96.
[5] Weng L,Quinlivan E,Gong Y,et al. Association of branched and aromatic amino acids levels with meta-bolic syndrome and impaired fasting glucose in hyperten-sive patients[J]. Metab Syndr Relat Disord,2015,13(5):195-202.
[6] Wang Q,Holmes MV,Davey Smith G,et al. Genetic support for a causal role of insulin resistance on circulating branchedchain amino acids andinflamma-tion[J]. Diabetes Care,2017,40(12):79-86.
[7] Klein MS,Shearer J. Metabolomics and type 2 diabetes:Translatingbasicresearchintoclinicalapplication[J]. Diabetes Res,2016,38(5):92-98.
[8] Fiehn O,Garvey T,Newman JW,et al. Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type2 diabetic obese African-American women[J]. PLOS One,2010,5(12):15-23.
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[12] Yu D,Moore SC,Matthews CE,et al. Plasma metabo-lomic profiles in association with type 2 diabetes risk and prevalence in Chinese adults[J]. Metabolomics,2016,1(12):3.
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[15] Adeva-Andany MM,López-Maside L,Donapetry-García C,et al. Enzymes involved in branched-chain amino acid metabolism in humans[J]. Amino Acids,2017,49(2):1005-1028.
[16] Zhang S,Zeng X,Ren M,et al. Novel meta-bolic and physiological functions of branched chain amino acids:A review[J].J Anim Sci Biotechnol,2017,8:10.
[17] Gar C,Rottenkolber M,Prehn C,et al. Serum and plasma amino acids as markers of prediabetes,insulin resistance, and incident diabetes[J]. Crit Rev Clin Lab Sci,2017,12(6):1-12.
[18] Gojda J,StrakováR,PlíhalováA,et al. Increased incre-tin but not insulin response after oral versus intravenous branched chain amino acids[J]. Ann Nutr Metab, 2017, 70(2):293-302.
[19] Fukagawa NK,Minaker KL,Rowe JW,et al. Insulin-mediated reduction of whole body protein breakdown. Dose-response effects on leucine metabolism in postab-sorptive men[J]. Clin Invest,1985,76(6):2306-2311.
[20] Tessari P. Effects of insulin on whole-body and regional amino acid metabolism[J]. Diab Metab Rev,1994,10(4):253-285.
[21] Felig P,Marliss E,Cahill G,et al. Plasma amino acid levels and insulin secretion in obesity[J]. Med,1969,281(3):811-816.
[22] Luzi L,Petrides AS,De Fronzo RA. Different sensitivity of glucose and amino acid metabolism to insulin in NIDDM[J]. Diabetes,1993,42(12):1868-1877.
[23] Nagao K,Yamakado M. The role of amino acid profiles in diabetes risk assessment[J]. Curr Opin Clin Nutr Metab Care,2016,19(5):28-35.
[24] Hernández-Alvarez MI,Díaz-Ramos A,Berdasco M,et al.Early-onset and classical forms of type 2 diabetes show impaired expression of genes involved in muscle branched-chain amino acids metabolism[J]. Sci Rep,2017,7(1):13850.
[25] Lotta LA,Scott RA,Sharp SJ,et al. Genetic predisposition to an impaired metabolism of the branched-chain amino acids and risk of type 2 diabetes:A Mende-lian randomisation analysis[J]. PLOS Med,2016,13(11):e1002179.
[26] Mahendran Y,Jonsson A,Have CT,et al. Genetic evi-dence of a causal effect of insulin resistance on branched-chain amino acid levels[J]. Diabetologia,2017,60(3):873-878.
[27] O’ Connell TM. The complex role of branched chain amino acids in diabetes and cancer[J]. Metabolites,2013,3(4):931-945.
[28] Newgard CB,An J,Bain JR,et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resis-tance[J]. Cell Metab,2009,9(4):311-326.
[29] Lu J,Xie G,Jia W,et al. Insulin resistance and the metabolism of branched-chain amino acids[J]. Front Med,2013,7(1):53-59.
[30] Ly Lynch CJ,Adams SH. Branched-chain amino acids in metabolic signalling and insulin resistance[J]. Nat Rev Endocrinol,2014,10(12):723-736.
[31] Shin AC,Fasshauer M,Filatova N,et al. Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism[J]. Cell Metab,2014,20(5):898-909.
[32] Cummings NE,Williams EM,Kasza I,et al. Restoration of metabolic health by decreased consumption of branched-chain amino acids[J]. Physiol,2017,596(4):623-645.
[33] Nagata C,Nakamura K,Wada K,et al. Branched-chain amino acid intake and the risk of diabetes in a Japanese community:The Takayama study[J]. Am J Epidemiol,2013,178(8):1226-32.
[34] Zheng Y,Li Y,Qi Q,et al. Cumulative consumption of branched-chain amino acids and incidence of type 2 dia-betes[J]. Int J Epidemiol,2016,45(5):1482-1492.
[35] Isanejad M,La Croix AZ,Thomson CA,et al. Branched-chain amino acid, meat intake and risk of type 2 diabetes in the Women’ s Health Initiative[J]. Br J Nutr, 2017, 17(11):1523-1530.
[36] Asghari G,Farhadnejada H,Teymoori F,et al. High dietary intakes of branched-chain amino acids is associated with increased risk of insulin resistance in adults[J]. Diabetes,2018,10(5):357-364.
[37] Magkos F,Bradley D,Schweitzer GG,et al. Effect of Rouxen-Y gastric bypass and laparoscopic adjustable gastric banding on branched-chain amino acid metabo-lism[J]. Diabetes,2016,103(1):61-65.
[38] Lips MA,Van Klinken JB,van Harmelen V,et al. Roux-enY gastric bypass surgery, but not calorie restriction, reduces plasma branched-chain amino acids in obese women independent of weight loss or the pres-ence of type 2 diabetes[J]. Diabetes Care,2014,37(12):3150-3156.
[39] Saad MJ,Santos A,Prada PO. Linking gut microbiota and inflammation to obesity and insulin resistance[J]. Phys-iology(Bethesda),2016,31(4):283-293.
[40] Yoon MS. The emerging role of branched-chain amino acids in insulin resistance and metabolism[J]. Forum Nutr,2016,8(7):405.
[41] Kappel BA,Lehrke M,Schütt K,et al. Effect of empagli-flozin on the metabolic signature of patients with type 2 diabetes mellitus and cardiovascular disease[J]. Circula-tion,2017,136(2):69-72.
[2] Okekunle AP,Li Y,Liu L,et al. Abnormal circulating amino acid profiles in multiple metabolic disorders[J]. Dia-betes Res Clin Pract,2017,132(7):45-58.
[3] Hu W,Sun L,Gong Y,et al. Relationship between branchedchain amino acids,metabolic syndrome,and cardiovascular risk profile in a chinese population:A cross-sectional study[J]. Int J Endocrinol,2016:8173905.
[4] Batch BC,Shah SH,Newgard CB,et al. Branched chain amino acids are novel biomarkers for discrimination of metabolic wellness[J]. Metabolism,2013,62(7):91-96.
[5] Weng L,Quinlivan E,Gong Y,et al. Association of branched and aromatic amino acids levels with meta-bolic syndrome and impaired fasting glucose in hyperten-sive patients[J]. Metab Syndr Relat Disord,2015,13(5):195-202.
[6] Wang Q,Holmes MV,Davey Smith G,et al. Genetic support for a causal role of insulin resistance on circulating branchedchain amino acids andinflamma-tion[J]. Diabetes Care,2017,40(12):79-86.
[7] Klein MS,Shearer J. Metabolomics and type 2 diabetes:Translatingbasicresearchintoclinicalapplication[J]. Diabetes Res,2016,38(5):92-98.
[8] Fiehn O,Garvey T,Newman JW,et al. Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type2 diabetic obese African-American women[J]. PLOS One,2010,5(12):15-23.
[9] Chen T,Ni Y,Ma X,etal. Branched-chain and aromatic amino acid profiles and diabetes risk in Chinese popula-tions[J].Sci Rep,2016,5(6):20594.
[10] Guasch-FerréM,Hruby A,Toledo E,et al. Metabolo-mics in prediabetes and diabetes:A systematic review and meta-analysis[J]. Diabetes Care,2016,39(5):833-846.
[11] Kujala UM,Peltonen M,Laine MK,et al. Branched-chain amino acid levels are related with surrogates of dis-turbed lipid metabolism among older men[J]. Front Med,2016,3:57.
[12] Yu D,Moore SC,Matthews CE,et al. Plasma metabo-lomic profiles in association with type 2 diabetes risk and prevalence in Chinese adults[J]. Metabolomics,2016,1(12):3.
[13] Yang R,Dong J,Zhao H,et al. Association of branchedchain amino acids with carotid intima-media thickness and coronary artery disease risk factors[J]. PLOS One,2014,9(6):e99598.
[14] Bhattacharya S,Granger CB,Craig D,et al. Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery dis-ease in patients referred for cardiac catheterization[J]. Ath-erosclerosis,2014,232(1):191-196.
[15] Adeva-Andany MM,López-Maside L,Donapetry-García C,et al. Enzymes involved in branched-chain amino acid metabolism in humans[J]. Amino Acids,2017,49(2):1005-1028.
[16] Zhang S,Zeng X,Ren M,et al. Novel meta-bolic and physiological functions of branched chain amino acids:A review[J].J Anim Sci Biotechnol,2017,8:10.
[17] Gar C,Rottenkolber M,Prehn C,et al. Serum and plasma amino acids as markers of prediabetes,insulin resistance, and incident diabetes[J]. Crit Rev Clin Lab Sci,2017,12(6):1-12.
[18] Gojda J,StrakováR,PlíhalováA,et al. Increased incre-tin but not insulin response after oral versus intravenous branched chain amino acids[J]. Ann Nutr Metab, 2017, 70(2):293-302.
[19] Fukagawa NK,Minaker KL,Rowe JW,et al. Insulin-mediated reduction of whole body protein breakdown. Dose-response effects on leucine metabolism in postab-sorptive men[J]. Clin Invest,1985,76(6):2306-2311.
[20] Tessari P. Effects of insulin on whole-body and regional amino acid metabolism[J]. Diab Metab Rev,1994,10(4):253-285.
[21] Felig P,Marliss E,Cahill G,et al. Plasma amino acid levels and insulin secretion in obesity[J]. Med,1969,281(3):811-816.
[22] Luzi L,Petrides AS,De Fronzo RA. Different sensitivity of glucose and amino acid metabolism to insulin in NIDDM[J]. Diabetes,1993,42(12):1868-1877.
[23] Nagao K,Yamakado M. The role of amino acid profiles in diabetes risk assessment[J]. Curr Opin Clin Nutr Metab Care,2016,19(5):28-35.
[24] Hernández-Alvarez MI,Díaz-Ramos A,Berdasco M,et al.Early-onset and classical forms of type 2 diabetes show impaired expression of genes involved in muscle branched-chain amino acids metabolism[J]. Sci Rep,2017,7(1):13850.
[25] Lotta LA,Scott RA,Sharp SJ,et al. Genetic predisposition to an impaired metabolism of the branched-chain amino acids and risk of type 2 diabetes:A Mende-lian randomisation analysis[J]. PLOS Med,2016,13(11):e1002179.
[26] Mahendran Y,Jonsson A,Have CT,et al. Genetic evi-dence of a causal effect of insulin resistance on branched-chain amino acid levels[J]. Diabetologia,2017,60(3):873-878.
[27] O’ Connell TM. The complex role of branched chain amino acids in diabetes and cancer[J]. Metabolites,2013,3(4):931-945.
[28] Newgard CB,An J,Bain JR,et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resis-tance[J]. Cell Metab,2009,9(4):311-326.
[29] Lu J,Xie G,Jia W,et al. Insulin resistance and the metabolism of branched-chain amino acids[J]. Front Med,2013,7(1):53-59.
[30] Ly Lynch CJ,Adams SH. Branched-chain amino acids in metabolic signalling and insulin resistance[J]. Nat Rev Endocrinol,2014,10(12):723-736.
[31] Shin AC,Fasshauer M,Filatova N,et al. Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism[J]. Cell Metab,2014,20(5):898-909.
[32] Cummings NE,Williams EM,Kasza I,et al. Restoration of metabolic health by decreased consumption of branched-chain amino acids[J]. Physiol,2017,596(4):623-645.
[33] Nagata C,Nakamura K,Wada K,et al. Branched-chain amino acid intake and the risk of diabetes in a Japanese community:The Takayama study[J]. Am J Epidemiol,2013,178(8):1226-32.
[34] Zheng Y,Li Y,Qi Q,et al. Cumulative consumption of branched-chain amino acids and incidence of type 2 dia-betes[J]. Int J Epidemiol,2016,45(5):1482-1492.
[35] Isanejad M,La Croix AZ,Thomson CA,et al. Branched-chain amino acid, meat intake and risk of type 2 diabetes in the Women’ s Health Initiative[J]. Br J Nutr, 2017, 17(11):1523-1530.
[36] Asghari G,Farhadnejada H,Teymoori F,et al. High dietary intakes of branched-chain amino acids is associated with increased risk of insulin resistance in adults[J]. Diabetes,2018,10(5):357-364.
[37] Magkos F,Bradley D,Schweitzer GG,et al. Effect of Rouxen-Y gastric bypass and laparoscopic adjustable gastric banding on branched-chain amino acid metabo-lism[J]. Diabetes,2016,103(1):61-65.
[38] Lips MA,Van Klinken JB,van Harmelen V,et al. Roux-enY gastric bypass surgery, but not calorie restriction, reduces plasma branched-chain amino acids in obese women independent of weight loss or the pres-ence of type 2 diabetes[J]. Diabetes Care,2014,37(12):3150-3156.
[39] Saad MJ,Santos A,Prada PO. Linking gut microbiota and inflammation to obesity and insulin resistance[J]. Phys-iology(Bethesda),2016,31(4):283-293.
[40] Yoon MS. The emerging role of branched-chain amino acids in insulin resistance and metabolism[J]. Forum Nutr,2016,8(7):405.
[41] Kappel BA,Lehrke M,Schütt K,et al. Effect of empagli-flozin on the metabolic signature of patients with type 2 diabetes mellitus and cardiovascular disease[J]. Circula-tion,2017,136(2):69-72.