韩绍伦;李剑;王子健;

• 1:北京师范大学水科学研究院地下水污染控制与修复教育部工程研究中心
• 2:中国科学院生态环境研究中心

摘要(Abstract)：

不断升高的糖尿病发病率在全球范围内引起广泛关注,流行病学调查显示糖尿病发病率的增加与环境内分泌干扰化合物使用量增大之间存在显著相关,环境内分泌干扰化合物可能增加糖尿病发病风险,是影响糖尿病的危险因素。在此背景下,综述了环境内分泌干扰化合物暴露与糖尿病发病之间的流行病学关系;环境内分泌干扰化合物暴露对胰岛β细胞胰岛素分泌的调节、高胰岛素效应及其潜在的作用机理,表明影响胰岛素分泌是环境内分泌干扰化合物调节代谢,诱发糖尿病的重要作用机制。

关键词(KeyWords)： 环境内分泌干扰物;作用机理;糖尿病;胰岛素;雌激素受体

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学青年基金(41001351);; 高等学校博士学科点专项科研基金资助课题(20100003120024)

作者(Author): 韩绍伦;李剑;王子健;

Email:

DOI:

参考文献(References)：

• [1]李剑,马梅,王子健.环境内分泌干扰物的作用机理及其生物检测方法[J].环境监控与预警,2010,2(3):18-25Li J,Ma M,Wang Z J.Action mechanisms and bioassays of environmental endocrine disrupting chemicals[J].Environmental Monitoring and Forewarnming,2010,2(3):18-25(in Chinese)
• [2]刘先利,刘彬,邓南圣.环境内分泌干扰物研究进展[J].上海环境科学,2003,22(1):57-62Liu X L,Liu B,Deng N S.Study progress of environmental endocrine disruptors[J].Shanghai Environmental Sciences 2003,22(1):57-62(in Chinese)
• [3]Diamanti-Kandarakis E,Bourguignon J P,Giudice L C,et al.Endocrine-disrupting chemicals:An Endocrine Society scientific statement[J].Endocrine Reviews,2009,30(4):293-342
• [4]Alonso-Magdalena P,Quesada I,Nadal A.Endocrine disruptors in the etiology of type 2 diabetes mellitus[J].Nature Reviews Endocrinology,2011,7(6):346-353
• [5]代庆红,王忠东.中国糖尿病的现状调查[J].中国医学指南,2011,9(13):206-208
• [6]中华医学会糖尿病学分会.中国2型糖尿病防治指南(2010年版)[J].中国糖尿病杂志,2012,20(1):1-37
• [7]Williams E D,Tapp R J,Magliano D J,et al.Health behaviors,socioeconomic status and diabetes incidence:The Australian Diabetes Obesity and Lifestyle Study[J].Diabetologia,2010,53(12):2538-2545
• [8]Finucane M M,Stevens G A,Cowan M J,et al.National,regional,and global trends in body-mass index since1980:Systematic analysis of health examination surveys and epidemiological studies with 960 country years and9.1 million participants[J].Lancet,2011,377(9765):557-567
• [9]Zimmet P,Alberti K G M M,Shaw J,et al.Global and societal implications of the diabetes epidemic[J].Nature,2001,414(6865):782-787
• [10]Carpenter D O.Environmental contaminants as risk factors for developing diabetes[J].Reviews on Environmental Health,2008,23(1):59-74
• [11]vom Saal F S,Myers J P.Bisphenol A and risk of metabolic disorders[J].The Journal of the American Medical Association,2008,300(11):1353-1355
• [12]Rignell-Hydbom A,Lidfeldt J,Kiviranta H,et al.Exposure to p,p'-DDE:A risk factor for type 2 diabetes[J].PLoS one,2009,4:e7503
• [13]Lin C Y,Chen P C,Lin Y C,et al.Association among serum perfluoroalkyl chemicals,glucose homeostasis,and metabolic syndrome in adolescents and adults[J].Diabetes Care,2009,34(7):702-707
• [14]Lim J S,Lee D H,Jacobs D R Jr,et al.Association of brominated flame retardants with diabetes and metabolic syndrome in the U.S.population,2003-2004[J].Diabetes Care,2008,31(9):1802-1807
• [15]Park S K,Son H K,Lee S K,et al.Relationship between serum concentrations of organochlorine pesticides and metabolic syndrome among non-diabetic adults[J].Journey of Preventive Medicine and Public Health,2010,43(1):1-8
• [16]Lee D H,Lee I K,Song K,et al.A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes:Results from the National Health and Examination Survey 1999-2002[J].Diabetes Care,2006,29(7):1638-1644
• [17]Everett C J,Frithsen I,Player M.Relationship of polychlorinated biphenyls with type 2 diabetes and hypertension[J].Journal of Environmental Monitoring,2011,13(2):241-251
• [18]Uemura H,Arisawa K,Hiyoshi M.Prevalence of metabolic syndrome associated with body burden levels of dioxin andrelated compounds among Japan's general population[J].Environmental Health Perspectives,2009,117(4):568-573
• [19]Lang I A,Galloway T S,Scarlett A,et al.Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults[J].The Journal of the American Medical Association,2008,300(11):1303-1310
• [20]Stahlhut R W,van Wijngaarden E,Dye T D,et al.Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult U.S.males[J].Environmental Health Perspectives,2007,115(6):876-882
• [21]Hoppe A A,Carey G B.Polybrominated diphenyl ethers as endocrine disruptors of adipocyte metabolism[J].Obesity,2007,15(12):2942-2950
• [22]Alonso-Magdalena P,Morimoto S,Ripoll C,et al.The estrogenic effect of bisphenol A disrupts pancreatic beta-cell function in vivo and induces insulin resistance[J].Environmental Health Perspectives,2006,114(1):106-112
• [23]Batista T M,Alonso M P,Vieira E,et al.Short-term treatment with bisphenol-A leads to metabolic abnormalities in adult male mice[J].PloS one,2012,7(3):e33814
• [24]Kamath V,Rajini P S.Altered glucose homeostasis and oxidative impairment in pancreas of rats subjected to dimethoate intoxication[J].Toxicology,2007,231(2 3):137-146
• [25]Muoio D M,Newgard C B.Molecular and metabolic mechanisms of insulin resistance andβ-cell failure in type 2 diabetes[J].Nat Rev,2008,9:193-205
• [26]Alonso-Magdalena P,Ropero A B,Carrera M P,et al.Pancreatic insulin content regulation by the estrogen receptor ERα[J].PLoS oNE,2008,3(4):e2069
• [27]Hectors T L M,Vanparys C,van der Ven K,et al.Environmental pollutants and type 2 diabetes:A review of mechanisms that can disrupt beta cell function[J].Diabetologia,2011,54(6):1273-1290
• [28]Nadal A,Alonso-Magdalena P,Soriano S,et al.The pancreatic beta-cell as a target of estrogens and xenoestrogens:Implications for blood glucose homeostasis and diabetes[J].Molecular and Cellular Endocrinology,2009,304(1-2):63-68
• [29]Prado C L,Pugh-Bemard A E,Elghazi L,et al.Ghrelin:Cells replace insulin-producing beta cells in two mouse models of pancreas development[J].Proceedings of the National Academy of Sciences of the United States of America,2004,101(9):2924-2929
• [30]Rutter G A.Nutrient-secretion coupling in the pancreatic isletβ-cell:Recent advances[J].Molecular Aspects of Medicine,2001,22(6):247-284
• [31]Chen J Q,Brown T R,Russo J.Regulation of energy metabolism pathways by estrogens and estrogenic chemicals and potential implications in obesity associated with increased exposure to endocrine disruptors[J].Biochimica et Biophysica Acta,2009,1793(7):1128-1143
• [32]Louet J F,LeMay C,Mauvais-Jarvis F.Antidiabetic actions of estrogen:Insights from humans and genetic mouse models[J].Current Atherosclerosis Reports,2004,6(3):180-185
• [33]Contreras J L,Smyth C A,Bilbao G,et al.17beta-Estradiol protects isolated human pancreatic islets against proinflammatory cytokine-induced cell death:Molecular mechanisms and islet functionality[J].Transplantation,2002,74(9):1252-1259
• [34]May C L,Chu K,Hu M,et al.Estrogens protect pancreaticβ-cells from apoptosis and prevent insulin-deficient diabetes mellitus in mice[J].Proceedings of the National Academy of Sciences of the United States of America,2006,103(24):9232-9237
• [35]Balhuizen A,Kumar R,Amisten S,et al.Activation of G protein-coupled receptor 30 modulates hormone secretion and counteracts cytokine-induced apoptosis in pancreatic islets of female mice[J].Molecular and Cellular Endocrinology,2010,320(1 2):16-24
• [36]Song L,Xia W,Zhou Z,et al.Low-level phenolic estrogen pollutants impair islet morphology andβ-cell function in isolated rat islets[J].Journal of Endocrinology,2012,215(2):303-311
• [37]Soriano1 S,Alonso-Magdalena1 P,García-Areívalo M,et al.Rapid insulinotropic action of low doses of bisphenol-A on mouse and human islets of Langerhans:Role of estrogen receptorβ[J].PLoS one,2012,7(2):e31109
• [38]Newbold R R.Developmental exposure to endocrine disruptors and the obesity epidemic[J].Reproductive Toxicology,2007,23(3):290-296
• [39]Lin Y,Wei J,Li Y,et al.Developmental exposure to di(2-ethylhexyl)phthalate impairs endocrine pancreas and leads to long-term adverse effects on glucose homeostasis in the rat[J].American Journal of Physiology Endocrinology and Metabolism,2011,301(3):527-538
• [40]Gayathri N S,Dhanya C R,Indu A R,et al.Changes in somehormones by low doses of di(2-ethylhexyl)phthalate(DEHP),a commonly used plasticizer in PVC blood storage bags and medical tubing[J].Indian Journal of Medical Research,2004,119(4):139-144
• [41]Novelli M,Piaggi S,Tata V D.2,3,7,8-Tetrachlorodibenzo-pdioxin-induced impairment of glucose-stimulated insulin secretion in isolated rat pancreatic islets[J].Toxicology Letters,2005,156(2):307-314
• [42]Piaggi S,Novelli M,Martino L,et al.Cell death and impairment of glucose-stimulated insulin secretion induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD)in theβ-cell line INS-1E[J].Toxicology and Applied Pharmacology,2007,220(3):333-340
• [43]Ghafour-Rashidi Z,Dermenaki-Farahani E,Aliahmadi A,et al.Protection by cAMP and cGMP phosphodiesterase inhibitors of diazinon-induced hyperglycemia and oxidative/nitrosative stress in rat Langerhans is lets cells:Molecular evidence for involvement of non-cholinergic mechanisms[J].Pesticide Biochemistry Physiology,2007,87(3):261-270
• [44]Pournourmohammadi S,Ostad S N,Azizi E,et al.Induction of insulin resistance by malathion:Evidence for disrupted islets cells metabolism and mitochondrial dysfunction[J].Pesticide Biochemistry Physiology,2007,88(3):346-352
• [45]Livingstone C,Collison M.Sex steroids and insulin resistance[J].Clinical Science,2002,102(2):151-166
• [46]Zsarnovszky A,Le H H,Wang H S,et al.Ontogeny of rapid estrogen-mediated extracellular signal-regulated kinase signaling in the rat cerebellar cortex:Potent nongenomic agonist and endocrine disrupting activity of the xenoestrogen bisphenol A[J].Endocrinology,2005,146(12):5388-5396
• [47]董永明,张铭,林显光,等.钙离子信号对胰岛素分泌的调控[J].现代生物医学进展,2008,8(5):937-939Dong Y M,Zhang M,Lin X G,et al.The mechanism of calcium signaling regulating insulin secretion[J].Progress in Modern Biomedicine,2008,8(5):937-939(in Chinese)
• [48]Wong W P,Tiano J P,Liu S,et al.Extranuclear estrogen receptor-alpha stimulates Neuro D1 binding to the insulin promoter and favors insulin synthesis[J].Proceedings of the National Academy of Sciences of the United States of America,2010,107(29):13057-13062
• [49]赵晓民,徐小明.雌激素受体及其作用机制[J].西北农林科技大学学报:自然科学版,2004,32(12):154-158Zhao X M,Xu X M.Estrogen receptor and its molecular mechanism[J].Journal of Northwest A&F University(Natural Science Edition),2004,32(12):154-158(in Chinese)
• [50]Chetana M R,Daniel F C,Larry A S,et al.A transmembrane intracellular estrogen receptor mediates rapid cell signaling[J].Science,2005,307(5715):1625-1630
• [51]Kumar R,Balhuizen A,Amisten S,et al.Insulinotropic and antidiabetic effects of 17beta-estradiol and the GPR30 agonist G-1 on human pancreatic islets[J].Endocrinology,2011,152(7):2568-2579
• [52]Park C J,Zhao Z,Glidewell-Kenney C,et al.Genetic rescue of nonclassical ERalpha signaling normalizes energy balance in obese ERalpha-null mutant mice[J].Journal of Clinical Investigation,2011,121(2):604-612
• [53]Soriano S,Ropero B A,Alonso-Magdalena P,et al.Rapid regulation of KATPchannel activity by 17β-estradiol in pancreaticβ-cells involves the estrogen receptorβand the atrial natriuretic peptide receptor[J].Molecular Endocrinology,2009,23(12):1973-1982
• [54]Barros R P,Machado U F,Warner M,et al.Muscle GLUT4regulation by estrogen receptors ERβand ERα[J].Proceedings of the National Academy of Sciences of the United States of America,2006,103(5):1605-1608
• [55]Sharma G,Prossnitz E R.Mechanisms of estradiol-induced insulin secretion by the G protein-coupled estrogen receptor GPR30/GPER in pancreatic beta-cells[J].Endocrinology,2011,125(8):3030-3039
• [56]Liu S,Le May C,Wong W P,et al.Importance of extranuclear estrogen receptor-and membrane G protein-coupled estrogen receptor in pancreatic islet survival[J].Diabetes,2009,58(10):2292-2302
• [57]Quesada I,Fuentes E,Viso-leon M C,et al.Low doses of the endocrine disruptor bisphenol-A and the native hormone17β-estradiol rapidly activate transcription factor CREB[J].Federation of American Societies for Experimental Biology,2002,16(12):1671-1673
• [58]Wei J,Lin Y,Li Y,et al.Perinatal exposure to bisphenol A at reference dose predisposes offspring to metabolic syndrome in adult rats on a high-fat diet[J].Endocrinology,2011,152(8):1-12
• [59]Diaz-Sanchez V,Morimoto S,Morales A,et al.Androgen receptor in the rat pancreas:Genetic expression and steroid regulation[J].Pancreas,1995,11(3):241-245
• [60]崔玉倩.睾酮对胰岛β-细胞胰岛素分泌和凋亡的影响及机制[D].济南:山东大学,2012:3-5Cui Y Q.Effects and mechanisms of testosterone on glucose stimulated insulin secretion and cell apoptosis inβ-cells[D].Jinan:Shandong University,2012:3-5(in Chinese)
• [61]Fujiyoshi P T,Michalek J E,Matsumura F.Molecular epidemiologic evidence for diabetogenic effects of dioxin exposure in U.S.Air force veterans of the Vietnam war[J].Environmental Health Perspectives,2006,114(11):1677-1683
• [62]Sargis R M,Johnson D N,Choudhury R A,et al.Environmental endocrine disruptors promote adipogenesis in the3T3-L1 cell line through glucocorticoid receptor activation[J].Obesity,2010,18(7):1283-1288
• [63]Izquierdo-Vega J A,Soto C A,Sanchez-Pena L C,et al.Diabetogenic effects and pancreatic oxidative damage in rats subchronically exposed to arsenite[J].Toxicology Letters,2006,160(2):135-142
• [64]Chen Y W,Huang C F,Tsai K S,et al.Methylmercury induces pancreatic beta-cell apoptosis and dysfunction[J].Chemical Research in Toxicology,2006,19(8):1080-1085