{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:54:10Z","timestamp":1790470450053,"version":"4.1.0"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T00:00:00Z","timestamp":1574812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T00:00:00Z","timestamp":1574812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims\/hypothesis<\/jats:title><jats:p>Exposure to environmental pollution has been consistently linked to diabetes incidence in humans, but the potential causative mechanisms remain unclear. Given the critical role of regulated insulin secretion in maintaining glucose homeostasis, environmental chemicals that reach the endocrine pancreas and cause beta cell injury are of particular concern. We propose that cytochrome P450 (CYP) enzymes, which are involved in metabolising xenobiotics, could serve as a useful biomarker for direct exposure of islets to pollutants. Moreover, functional CYP enzymes in islets could also impact beta cell physiology. The aim of this study was to determine whether CYP1A enzymes are activated in islets following direct or systemic exposure to environmental pollutants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Immortalised liver (HepG2) and rodent pancreatic endocrine cell lines (MIN6, \u03b2TC-6, INS1, \u03b1-TC1, \u03b1-TC3), as well as human islets, were treated in vitro with known CYP1A inducers 2,3,7,8-tetrachlorodibenzo<jats:italic>-p-<\/jats:italic>dioxin (TCDD) and 3-methylcholanthrene (3-MC)<jats:italic>.<\/jats:italic>In addition, mice were injected with either a single high dose of TCDD or multiple low doses of TCDD in vivo<jats:italic>,<\/jats:italic>and islets were isolated 1, 7 or 14\u00a0days later.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CYP1A enzymes were not activated in any of the immortalised beta or alpha cell lines tested. However, both 3-MC and TCDD potently induced<jats:italic>CYP1A1<\/jats:italic>gene expression and modestly increased CYP1A1 enzyme activity in human islets after 48\u00a0h. The induction of<jats:italic>CYP1A1<\/jats:italic>in human islets by TCDD was prevented by cotreatment with a cytokine mixture. After a systemic single high-dose TCDD injection, CYP1A1 enzyme activity was induced in mouse islets ~2-fold, ~40-fold and ~80-fold compared with controls after 1, 7 and 14\u00a0days, respectively, in vivo. Multiple low-dose TCDD exposure in vivo also caused significant upregulation of<jats:italic>Cyp1a1<\/jats:italic>in mouse islets. Direct TCDD exposure to human and mouse islets in vitro resulted in suppressed glucose-induced insulin secretion. A single high-dose TCDD injection resulted in lower plasma insulin levels, as well as a pronounced increase in beta cell death.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions\/interpretation<\/jats:title><jats:p>Transient exposure to TCDD results in long-term upregulation of CYP1A1 enzyme activity in islets. This provides evidence for direct exposure of islets to lipophilic pollutants in vivo and may have implications for islet physiology.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s00125-019-05035-0","type":"journal-article","created":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T17:03:41Z","timestamp":1574874221000},"page":"162-178","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Functional cytochrome P450 1A enzymes are induced in mouse and human islets following pollutant exposure"],"prefix":"10.1007","volume":"63","author":[{"given":"Muna","family":"Ibrahim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin M.","family":"MacFarlane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geronimo","family":"Matteo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam P.","family":"Hoyeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayleigh R. C.","family":"Rick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salar","family":"Farokhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine M.","family":"Copley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"O\u2019Dwyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Bruin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,27]]},"reference":[{"key":"5035_CR1","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.envpol.2015.12.019","volume":"217","author":"DJ McGoldrick","year":"2016","unstructured":"McGoldrick DJ, Murphy EW (2016) Concentration and distribution of contaminants in lake trout and walleye from the Laurentian Great Lakes (2008-2012). Environ Pollut 217:85\u201396. https:\/\/doi.org\/10.1016\/j.envpol.2015.12.019","journal-title":"Environ Pollut"},{"key":"5035_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.envpol.2016.05.035","volume":"217","author":"H Hung","year":"2016","unstructured":"Hung H, Katsoyiannis AA, Guardans R (2016) Ten years of global monitoring under the Stockholm Convention on Persistent Organic Pollutants (POPs): trends, sources and transport modelling. Environ Pollut 217:1\u20133. https:\/\/doi.org\/10.1016\/j.envpol.2016.05.035","journal-title":"Environ Pollut"},{"key":"5035_CR3","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.envres.2014.07.023","volume":"134","author":"J Kumar","year":"2014","unstructured":"Kumar J, Lind L, Salihovic S, van Bavel B, Ingelsson E, Lind PM (2014) Persistent organic pollutants and liver dysfunction biomarkers in a population-based human sample of men and women. Environ Res 134:251\u2013256. https:\/\/doi.org\/10.1016\/j.envres.2014.07.023","journal-title":"Environ Res"},{"issue":"3","key":"5035_CR4","doi-asserted-by":"publisher","first-page":"2160","DOI":"10.1007\/s11356-015-4479-6","volume":"23","author":"JT Perkins","year":"2016","unstructured":"Perkins JT, Petriello MC, Newsome BJ, Hennig B (2016) Polychlorinated biphenyls and links to cardiovascular disease. Environ Sci Pollut Res Int 23(3):2160\u20132172. https:\/\/doi.org\/10.1007\/s11356-015-4479-6","journal-title":"Environ Sci Pollut Res Int"},{"key":"5035_CR5","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.envint.2012.11.005","volume":"52","author":"M Gascon","year":"2013","unstructured":"Gascon M, Morales E, Sunyer J, Vrijheid M (2013) Effects of persistent organic pollutants on the developing respiratory and immune systems: a systematic review. Environ Int 52:51\u201365. https:\/\/doi.org\/10.1016\/j.envint.2012.11.005","journal-title":"Environ Int"},{"issue":"2","key":"5035_CR6","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1111\/j.1742-7843.2007.00190.x","volume":"102","author":"I Hertz-Picciotto","year":"2008","unstructured":"Hertz-Picciotto I, Park HY, Dostal M, Kocan A, Trnovec T, Sram R (2008) Prenatal exposures to persistent and non-persistent organic compounds and effects on immune system development. Basic Clin Pharmacol Toxicol 102(2):146\u2013154. https:\/\/doi.org\/10.1111\/j.1742-7843.2007.00190.x","journal-title":"Basic Clin Pharmacol Toxicol"},{"issue":"2","key":"5035_CR7","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.mce.2011.09.005","volume":"355","author":"M Boas","year":"2012","unstructured":"Boas M, Feldt-Rasmussen U, Main KM (2012) Thyroid effects of endocrine disrupting chemicals. Mol Cell Endocrinol 355(2):240\u2013248. https:\/\/doi.org\/10.1016\/j.mce.2011.09.005","journal-title":"Mol Cell Endocrinol"},{"issue":"4","key":"5035_CR8","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1080\/026520300283351","volume":"17","author":"LS Birnbaum","year":"2000","unstructured":"Birnbaum LS, Tuomisto J (2000) Non-carcinogenic effects of TCDD in animals. Food Addit Contam 17(4):275\u2013288. https:\/\/doi.org\/10.1080\/026520300283351","journal-title":"Food Addit Contam"},{"issue":"11","key":"5035_CR9","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1093\/aje\/153.11.1031","volume":"153","author":"PA Bertazzi","year":"2001","unstructured":"Bertazzi PA, Consonni D, Bachetti S et al (2001) Health effects of dioxin exposure: a 20-year mortality study. Am J Epidemiol 153(11):1031\u20131044. https:\/\/doi.org\/10.1093\/aje\/153.11.1031","journal-title":"Am J Epidemiol"},{"issue":"8","key":"5035_CR10","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.2337\/dc07-2449","volume":"31","author":"SL Wang","year":"2008","unstructured":"Wang SL, Tsai PC, Yang CY, Guo YL (2008) Increased risk of diabetes and polychlorinated biphenyls and dioxins: a 24-year follow-up study of the Yucheng cohort. Diabetes Care 31(8):1574\u20131579. https:\/\/doi.org\/10.2337\/dc07-2449","journal-title":"Diabetes Care"},{"issue":"Suppl 2","key":"5035_CR11","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1289\/ehp.98106645","volume":"106","author":"J Vena","year":"1998","unstructured":"Vena J, Boffetta P, Becher H et al (1998) Exposure to dioxin and nonneoplastic mortality in the expanded IARC international cohort study of phenoxy herbicide and chlorophenol production workers and sprayers. Environ Health Perspect 106(Suppl 2):645\u2013653","journal-title":"Environ Health Perspect"},{"issue":"4","key":"5035_CR12","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1136\/oem.56.4.270","volume":"56","author":"GM Calvert","year":"1999","unstructured":"Calvert GM, Sweeney MH, Deddens J, Wall DK (1999) Evaluation of diabetes mellitus, serum glucose, and thyroid function among United States workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Occup Environ Med 56(4):270\u2013276. https:\/\/doi.org\/10.1136\/oem.56.4.270","journal-title":"Occup Environ Med"},{"key":"5035_CR13","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.envres.2014.04.027","volume":"133","author":"SW Yi","year":"2014","unstructured":"Yi SW, Hong JS, Ohrr H, Yi JJ (2014) Agent Orange exposure and disease prevalence in Korean Vietnam veterans: the Korean veterans health study. Environ Res 133:56\u201365. https:\/\/doi.org\/10.1016\/j.envres.2014.04.027","journal-title":"Environ Res"},{"issue":"3","key":"5035_CR14","doi-asserted-by":"publisher","first-page":"149","DOI":"10.2486\/indhealth.41.149","volume":"41","author":"JS Kim","year":"2003","unstructured":"Kim JS, Lim HS, Cho SI, Cheong HK, Lim MK (2003) Impact of Agent Orange exposure among Korean Vietnam veterans. Ind Health 41(3):149\u2013157. https:\/\/doi.org\/10.2486\/indhealth.41.149","journal-title":"Ind Health"},{"issue":"3","key":"5035_CR15","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1097\/00001648-199705000-00005","volume":"8","author":"GL Henriksen","year":"1997","unstructured":"Henriksen GL, Ketchum NS, Michalek JE, Swaby JA (1997) Serum dioxin and diabetes mellitus in veterans of Operation Ranch Hand. Epidemiology 8(3):252\u2013258. https:\/\/doi.org\/10.1097\/00001648-199705000-00005","journal-title":"Epidemiology"},{"issue":"1","key":"5035_CR16","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1097\/00001648-200001000-00010","volume":"11","author":"MP Longnecker","year":"2000","unstructured":"Longnecker MP, Michalek JE (2000) Serum dioxin level in relation to diabetes mellitus among Air Force veterans with background levels of exposure. Epidemiology 11(1):44\u201348. https:\/\/doi.org\/10.1097\/00001648-200001000-00010","journal-title":"Epidemiology"},{"issue":"6","key":"5035_CR17","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1007\/s11892-013-0432-6","volume":"13","author":"CC Kuo","year":"2013","unstructured":"Kuo CC, Moon K, Thayer KA, Navas-Acien A (2013) Environmental chemicals and type 2 diabetes: an updated systematic review of the epidemiologic evidence. Curr Diab Rep 13(6):831\u2013849. https:\/\/doi.org\/10.1007\/s11892-013-0432-6","journal-title":"Curr Diab Rep"},{"issue":"9535","key":"5035_CR18","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/S0140-6736(06)69174-5","volume":"368","author":"M Porta","year":"2006","unstructured":"Porta M (2006) Persistent organic pollutants and the burden of diabetes. Lancet 368(9535):558\u2013559. https:\/\/doi.org\/10.1016\/S0140-6736(06)69174-5","journal-title":"Lancet"},{"issue":"6","key":"5035_CR19","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1289\/ehp.1104597","volume":"120","author":"KA Thayer","year":"2012","unstructured":"Thayer KA, Heindel JJ, Bucher JR, Gallo MA (2012) Role of environmental chemicals in diabetes and obesity: a National Toxicology Program workshop review. Environ Health Perspect 120(6):779\u2013789. https:\/\/doi.org\/10.1289\/ehp.1104597","journal-title":"Environ Health Perspect"},{"issue":"7","key":"5035_CR20","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.2337\/dc06-0543","volume":"29","author":"DH Lee","year":"2006","unstructured":"Lee DH, Lee IK, Song K et al (2006) A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Examination Survey 1999\u20132002. Diabetes Care 29(7):1638\u20131644. https:\/\/doi.org\/10.2337\/dc06-0543","journal-title":"Diabetes Care"},{"issue":"6","key":"5035_CR21","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.diabet.2013.01.006","volume":"39","author":"S Pal","year":"2013","unstructured":"Pal S, Blais JM, Robidoux MA et al (2013) The association of type 2 diabetes and insulin resistance\/secretion with persistent organic pollutants in two First Nations communities in northern Ontario. Diabetes Metab 39(6):497\u2013504. https:\/\/doi.org\/10.1016\/j.diabet.2013.01.006","journal-title":"Diabetes Metab"},{"issue":"3","key":"5035_CR22","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.envres.2006.11.002","volume":"103","author":"CJ Everett","year":"2007","unstructured":"Everett CJ, Frithsen IL, Diaz VA, Koopman RJ, Simpson WM Jr, Mainous AG 3rd (2007) Association of a polychlorinated dibenzo-p-dioxin, a polychlorinated biphenyl, and DDT with diabetes in the 1999\u20132002 National Health and Nutrition Examination Survey. Environ Res 103(3):413\u2013418. https:\/\/doi.org\/10.1016\/j.envres.2006.11.002","journal-title":"Environ Res"},{"issue":"4","key":"5035_CR23","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1210\/er.9013-1084","volume":"35","author":"DH Lee","year":"2014","unstructured":"Lee DH, Porta M, Jacobs DR Jr, Vandenberg LN (2014) Chlorinated persistent organic pollutants, obesity, and type 2 diabetes. Endocr Rev 35(4):557\u2013601. https:\/\/doi.org\/10.1210\/er.9013-1084","journal-title":"Endocr Rev"},{"issue":"7","key":"5035_CR24","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1289\/ehp.1205502","volume":"121","author":"KW Taylor","year":"2013","unstructured":"Taylor KW, Novak RF, Anderson HA et al (2013) Evaluation of the association between persistent organic pollutants (POPs) and diabetes in epidemiological studies: a national toxicology program workshop review. Environ Health Perspect 121(7):774\u2013783. https:\/\/doi.org\/10.1289\/ehp.1205502","journal-title":"Environ Health Perspect"},{"issue":"3","key":"5035_CR25","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/s00592-014-0674-z","volume":"52","author":"E Roh","year":"2015","unstructured":"Roh E, Kwak SH, Jung HS et al (2015) Serum aryl hydrocarbon receptor ligand activity is associated with insulin resistance and resulting type 2 diabetes. Acta Diabetol 52(3):489\u2013495. https:\/\/doi.org\/10.1007\/s00592-014-0674-z","journal-title":"Acta Diabetol"},{"issue":"10","key":"5035_CR26","doi-asserted-by":"publisher","first-page":"2669","DOI":"10.2337\/db17-0188","volume":"66","author":"YM Lee","year":"2017","unstructured":"Lee YM, Ha CM, Kim SA et al (2017) Low-dose persistent organic pollutants impair insulin secretory function of pancreatic \u03b2-cells: human and in vitro evidence. Diabetes 66(10):2669\u20132680. https:\/\/doi.org\/10.2337\/db17-0188","journal-title":"Diabetes"},{"issue":"8","key":"5035_CR27","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1007\/s00125-008-1066-0","volume":"51","author":"ME Jorgensen","year":"2008","unstructured":"Jorgensen ME, Borch-Johnsen K, Bjerregaard P (2008) A cross-sectional study of the association between persistent organic pollutants and glucose intolerance among Greenland Inuit. Diabetologia 51(8):1416\u20131422. https:\/\/doi.org\/10.1007\/s00125-008-1066-0","journal-title":"Diabetologia"},{"issue":"7","key":"5035_CR28","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.2337\/dc13-2329","volume":"37","author":"EL Dirinck","year":"2014","unstructured":"Dirinck EL, Dirtu AC, Govindan M, Covaci A, Van Gaal LF, Jorens PG (2014) Exposure to persistent organic pollutants: relationship with abnormal glucose metabolism and visceral adiposity. Diabetes Care 37(7):1951\u20131958. https:\/\/doi.org\/10.2337\/dc13-2329","journal-title":"Diabetes Care"},{"key":"5035_CR29","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.tox.2015.06.001","volume":"334","author":"R Mailloux","year":"2015","unstructured":"Mailloux R, Fu A, Florian M et al (2015) A Northern contaminant mixture impairs pancreas function in obese and lean JCR rats and inhibits insulin secretion in MIN6 cells. Toxicology 334:81\u201393. https:\/\/doi.org\/10.1016\/j.tox.2015.06.001","journal-title":"Toxicology"},{"issue":"2","key":"5035_CR30","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.toxlet.2004.12.004","volume":"156","author":"M Novelli","year":"2005","unstructured":"Novelli M, Piaggi S, De Tata V (2005) 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced impairment of glucose-stimulated insulin secretion in isolated rat pancreatic islets. Toxicol Lett 156(2):307\u2013314. https:\/\/doi.org\/10.1016\/j.toxlet.2004.12.004","journal-title":"Toxicol Lett"},{"key":"5035_CR31","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1002\/jat.1459","volume":"29","author":"H Kurita","year":"2009","unstructured":"Kurita H, Yoshioka W, Nishimura N, Kubota N, Kadowaki T, Tohyama C (2009) Aryl hydrocarbon receptor-mediated effects of TCDD on glucose-stimulated insulin secretion in mice. J Appl Toxicol 29:689\u2013694","journal-title":"J Appl Toxicol"},{"key":"5035_CR32","volume-title":"Adverse drug reactions. Handbook of Experimental Pharmacology","author":"PG Wells","year":"2010","unstructured":"Wells PG, Lee CJJ, McCallum GP, Perstin J, Harper PA (2010) Receptor- and reactive intermediate-mediated mechanisms of teratogenesis. In: Uetrecht J (ed) Adverse drug reactions. Handbook of Experimental Pharmacology, vol 196. Springer, Berlin, Heidelberg"},{"issue":"1","key":"5035_CR33","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/s0006-2952(99)00310-x","volume":"59","author":"DW Nebert","year":"2000","unstructured":"Nebert DW, Roe AL, Dieter MZ, Solis WA, Yang Y, Dalton TP (2000) Role of the aromatic hydrocarbon receptor and [Ah] gene battery in the oxidative stress response, cell cycle control, and apoptosis. Biochem Pharmacol 59(1):65\u201385. https:\/\/doi.org\/10.1016\/s0006-2952(99)00310-x","journal-title":"Biochem Pharmacol"},{"issue":"7","key":"5035_CR34","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1124\/dmd.107.015826","volume":"35","author":"Q Ma","year":"2007","unstructured":"Ma Q, Lu AY (2007) CYP1A induction and human risk assessment: an evolving tale of in vitro and in vivo studies. Drug Metab Dispos 35(7):1009\u20131016. https:\/\/doi.org\/10.1124\/dmd.107.015826","journal-title":"Drug Metab Dispos"},{"issue":"3","key":"5035_CR35","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1503\/jpn.120133","volume":"38","author":"S Miksys","year":"2013","unstructured":"Miksys S, Tyndale RF (2013) Cytochrome P450-mediated drug metabolism in the brain. J Psychiatry Neurosci 38(3):152\u2013163. https:\/\/doi.org\/10.1503\/jpn.120133","journal-title":"J Psychiatry Neurosci"},{"issue":"3","key":"5035_CR36","doi-asserted-by":"publisher","first-page":"291","DOI":"10.3109\/03602532.2014.900565","volume":"46","author":"U Gundert-Remy","year":"2014","unstructured":"Gundert-Remy U, Bernauer U, Blomeke B et al (2014) Extrahepatic metabolism at the body\u2019s internal-external interfaces. Drug Metab Rev 46(3):291\u2013324. https:\/\/doi.org\/10.3109\/03602532.2014.900565","journal-title":"Drug Metab Rev"},{"issue":"2","key":"5035_CR37","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1006\/taap.1995.1025","volume":"130","author":"JJ Diliberto","year":"1995","unstructured":"Diliberto JJ, Akubue PI, Luebke RW, Birnbaum LS (1995) Dose-response relationships of tissue distribution and induction of CYP1A1 and CYP1A2 enzymatic activities following acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice. Toxicol Appl Pharmacol 130(2):197\u2013208. https:\/\/doi.org\/10.1006\/taap.1995.1025","journal-title":"Toxicol Appl Pharmacol"},{"issue":"19","key":"5035_CR38","doi-asserted-by":"publisher","first-page":"11390","DOI":"10.1021\/acs.est.7b02830","volume":"51","author":"KP Lai","year":"2017","unstructured":"Lai KP, Wan HT, Ng AH, Li JW, Chan TF, Wong CK (2017) Transcriptomic and functional analyses on the effects of dioxin on insulin secretion of pancreatic islets and \u03b2-cells. Environ Sci Technol 51(19):11390\u201311400. https:\/\/doi.org\/10.1021\/acs.est.7b02830","journal-title":"Environ Sci Technol"},{"issue":"3","key":"5035_CR39","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/sj.bjp.0701139","volume":"121","author":"J Clarke","year":"1997","unstructured":"Clarke J, Flatt PR, Barnett CR (1997) Cytochrome P450 1A-like proteins expressed in the islets of Langerhans and altered pancreatic \u03b2-cell secretory responsiveness. Br J Pharmacol 121(3):389\u2013394. https:\/\/doi.org\/10.1038\/sj.bjp.0701139","journal-title":"Br J Pharmacol"},{"key":"5035_CR40","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1111\/j.1530-0277.1998.tb03679.x","volume":"22","author":"IG Kessova","year":"1998","unstructured":"Kessova IG, DeCarli LM, Lieber CS (1998) Inducibility of cytochromes P-4502E1 and P-4501A1 in the rat pancreas. Alcohol Clin Exp Res 22:501\u2013504","journal-title":"Alcohol Clin Exp Res"},{"issue":"42","key":"5035_CR41","doi-asserted-by":"publisher","first-page":"26261","DOI":"10.1074\/jbc.271.42.26261","volume":"271","author":"YH Chen","year":"1996","unstructured":"Chen YH, Tukey RH (1996) Protein kinase C modulates regulation of the CYP1A1 gene by the aryl hydrocarbon receptor. J Biol Chem 271(42):26261\u201326266. https:\/\/doi.org\/10.1074\/jbc.271.42.26261","journal-title":"J Biol Chem"},{"key":"5035_CR42","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1007\/s10126-015-9669-1","volume":"17","author":"H Xu","year":"2015","unstructured":"Xu H, Li C, Li Y et al (2015) Generation of Tg(cyp1a:gfp) transgenic zebrafish for development of a convenient and sensitive in vivo assay for aryl hydrocarbon receptor activity. Mar Biotechnol (NY) 17:831\u2013840","journal-title":"Mar Biotechnol (NY)"},{"issue":"16","key":"5035_CR43","doi-asserted-by":"crossref","first-page":"12118","DOI":"10.1016\/S0021-9258(17)32689-3","volume":"269","author":"DS Riddick","year":"1994","unstructured":"Riddick DS, Huang Y, Harper PA, Okey AB (1994) 2,3,7,8-Tetrachlorodibenzo-p-dioxin versus 3-methylcholanthrene: comparative studies of Ah receptor binding, transformation, and induction of CYP1A1. J Biol Chem 269(16):12118\u201312128","journal-title":"J Biol Chem"},{"key":"5035_CR44","unstructured":"National Institutes of Health (2006) NTP technical report on the toxicology and carcinogenesis studies of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in female Harlan Sprague-Dawley rats (gavage studies). NIH publication no. 06-4468. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park. Available from https:\/\/ntp.niehs.nih.gov\/ntp\/htdocs\/lt_rpts\/tr521.pdf. Accessed October 2019"},{"issue":"2","key":"5035_CR45","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1093\/toxsci\/kfm179","volume":"99","author":"DR Bell","year":"2007","unstructured":"Bell DR, Clode S, Fan MQ et al (2007) Relationships between tissue levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mRNAs, and toxicity in the developing male Wistar(Han) rat. Toxicol Sci 99(2):591\u2013604. https:\/\/doi.org\/10.1093\/toxsci\/kfm179","journal-title":"Toxicol Sci"},{"issue":"3","key":"5035_CR46","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.bbrc.2007.05.202","volume":"359","author":"N Dragin","year":"2007","unstructured":"Dragin N, Uno S, Wang B, Dalton TP, Nebert DW (2007) Generation of \u2018humanized\u2019 hCYP1A1_1A2_Cyp1a1\/1a2(-\/-) mouse line. Biochem Biophys Res Commun 359(3):635\u2013642. https:\/\/doi.org\/10.1016\/j.bbrc.2007.05.202","journal-title":"Biochem Biophys Res Commun"},{"issue":"3","key":"5035_CR47","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/j.taap.2004.01.014","volume":"196","author":"S Uno","year":"2004","unstructured":"Uno S, Dalton TP, Sinclair PR et al (2004) Cyp1a1(-\/-) male mice: protection against high-dose TCDD-induced lethality and wasting syndrome, and resistance to intrahepatocyte lipid accumulation and uroporphyria. Toxicol Appl Pharmacol 196(3):410\u2013421. https:\/\/doi.org\/10.1016\/j.taap.2004.01.014","journal-title":"Toxicol Appl Pharmacol"},{"issue":"3","key":"5035_CR48","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1007\/s00125-012-2784-x","volume":"56","author":"BM Tan","year":"2013","unstructured":"Tan BM, Zammit NW, Yam AO et al (2013) Baculoviral inhibitors of apoptosis repeat containing (BIRC) proteins fine-tune TNF-induced nuclear factor kappaB and c-Jun N-terminal kinase signalling in mouse pancreatic beta cells. Diabetologia 56(3):520\u2013532. https:\/\/doi.org\/10.1007\/s00125-012-2784-x","journal-title":"Diabetologia"},{"issue":"6","key":"5035_CR49","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1073\/pnas.0610690104","volume":"104","author":"S Kim","year":"2007","unstructured":"Kim S, Millet I, Kim HS et al (2007) NF-\u03baB prevents \u03b2 cell death and autoimmune diabetes in NOD mice. Proc Natl Acad Sci U S A 104(6):1913\u20131918. https:\/\/doi.org\/10.1073\/pnas.0610690104","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"5035_CR50","doi-asserted-by":"publisher","first-page":"2713","DOI":"10.2337\/db05-1430","volume":"55","author":"K Maedler","year":"2006","unstructured":"Maedler K, Schumann DM, Sauter N et al (2006) Low concentration of interleukin-1\u03b2 induces FLICE-inhibitory protein-mediated beta-cell proliferation in human pancreatic islets. Diabetes 55(10):2713\u20132722. https:\/\/doi.org\/10.2337\/db05-1430","journal-title":"Diabetes"},{"issue":"10","key":"5035_CR51","doi-asserted-by":"publisher","first-page":"6653","DOI":"10.1074\/jbc.M114.611111","volume":"290","author":"C Arous","year":"2015","unstructured":"Arous C, Ferreira PG, Dermitzakis ET, Halban PA (2015) Short term exposure of beta cells to low concentrations of interleukin-1beta improves insulin secretion through focal adhesion and actin remodeling and regulation of gene expression. J Biol Chem 290(10):6653\u20136669. https:\/\/doi.org\/10.1074\/jbc.M114.611111","journal-title":"J Biol Chem"},{"issue":"1","key":"5035_CR52","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1002\/jcp.20276","volume":"204","author":"G Papaccio","year":"2005","unstructured":"Papaccio G, Graziano A, D\u2019Aquino R, Valiante S, Naro F (2005) A biphasic role of nuclear transcription factor (NF)-\u03baB in the islet \u03b2-cell apoptosis induced by interleukin (IL)-1\u03b2. J Cell Physiol 204(1):124\u2013130. https:\/\/doi.org\/10.1002\/jcp.20276","journal-title":"J Cell Physiol"},{"issue":"9","key":"5035_CR53","doi-asserted-by":"publisher","first-page":"2356","DOI":"10.2337\/db06-1650","volume":"56","author":"JA Ehses","year":"2007","unstructured":"Ehses JA, Perren A, Eppler E et al (2007) Increased number of islet-associated macrophages in type 2 diabetes. Diabetes 56(9):2356\u20132370. https:\/\/doi.org\/10.2337\/db06-1650","journal-title":"Diabetes"},{"issue":"8","key":"5035_CR54","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1007\/s00125-009-1410-z","volume":"52","author":"SJ Richardson","year":"2009","unstructured":"Richardson SJ, Willcox A, Bone AJ, Foulis AK, Morgan NG (2009) Islet-associated macrophages in type 2 diabetes. Diabetologia 52(8):1686\u20131688. https:\/\/doi.org\/10.1007\/s00125-009-1410-z","journal-title":"Diabetologia"},{"issue":"3","key":"5035_CR55","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1007\/s00125-013-3116-5","volume":"57","author":"MJ Butcher","year":"2014","unstructured":"Butcher MJ, Hallinger D, Garcia E et al (2014) Association of proinflammatory cytokines and islet resident leucocytes with islet dysfunction in type 2 diabetes. Diabetologia 57(3):491\u2013501. https:\/\/doi.org\/10.1007\/s00125-013-3116-5","journal-title":"Diabetologia"},{"issue":"3","key":"5035_CR56","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1007\/s00125-017-4500-3","volume":"61","author":"M Solimena","year":"2018","unstructured":"Solimena M, Schulte AM, Marselli L et al (2018) Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes. Diabetologia 61(3):641\u2013657. https:\/\/doi.org\/10.1007\/s00125-017-4500-3","journal-title":"Diabetologia"},{"issue":"1","key":"5035_CR57","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/0041-008x(85)90314-x","volume":"78","author":"DE Chapman","year":"1985","unstructured":"Chapman DE, Schiller CM (1985) Dose-related effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in C57BL\/6J and DBA\/2J mice. Toxicol Appl Pharmacol 78(1):147\u2013157. https:\/\/doi.org\/10.1016\/0041-008x(85)90314-x","journal-title":"Toxicol Appl Pharmacol"},{"issue":"2","key":"5035_CR58","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1006\/taap.2001.9167","volume":"173","author":"AG Smith","year":"2001","unstructured":"Smith AG, Clothier B, Carthew P et al (2001) Protection of the Cyp1a2(-\/-) null mouse against uroporphyria and hepatic injury following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Appl Pharmacol 173(2):89\u201398. https:\/\/doi.org\/10.1006\/taap.2001.9167","journal-title":"Toxicol Appl Pharmacol"}],"container-title":["Diabetologia"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-019-05035-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00125-019-05035-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-019-05035-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T02:07:04Z","timestamp":1612663624000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00125-019-05035-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,27]]},"references-count":58,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["5035"],"URL":"https:\/\/doi.org\/10.1007\/s00125-019-05035-0","relation":{},"ISSN":["0012-186X","1432-0428"],"issn-type":[{"value":"0012-186X","type":"print"},{"value":"1432-0428","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,27]]},"assertion":[{"value":"14 May 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that there is no duality of interest associated with this manuscript.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Duality of interest"}}]}}