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Epidemiological and experimental data have shown that DEHP has a negative influence on glucose homeostasis. However, the evidence regarding the effect of maternal DEHP exposure on hepatic glucose homeostasis is scarce. Hence, we investigated whether DEHP exposure during gestation and lactation disrupts glucose homeostasis in the rat F<jats:sub>1<\/jats:sub> male offspring at adulthood. Pregnant rats were divided into three groups and administered with DEHP (10 and 100\u00a0mg\/kg\/day) or olive oil from gestational day 9 to postnatal day 21 (lactation period) through oral gavage. DEHP\u2010exposed offspring exhibited hyperglycemia, impaired glucose and insulin tolerances along with hyperinsulinemia at postnatal day 80. DEHP exposure significantly reduced the levels of insulin signaling molecules such as insulin receptors, IRS1, Akt and its phosphorylated forms. GSK3\u03b2 and FoxO1 proteins increased in DEHP\u2010exposed groups whereas its phosphorylated forms decreased. Treated groups showed decreased glycogen synthase activity and glycogen concentration. Glucose\u20106\u2010phosphatase and phosphoenolpyruvate carboxykinase mRNA level and enzyme activity increased in DEHP\u2010treated groups. The interaction between FoxO1\u2010glucose\u20106\u2010phosphatase and FoxO1\u2010phosphoenolpyruvate carboxykinase was also increased. This study suggests that DEHP exposure impairs insulin signal transduction and alters glucoregulatory events leading to the development of type 2 diabetes in F<jats:sub>1<\/jats:sub> male offspring.<\/jats:p>","DOI":"10.1002\/jat.3764","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T01:23:44Z","timestamp":1545182624000},"page":"751-763","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Maternal di\u2010(2\u2010ethylhexyl) phthalate exposure alters hepatic insulin signal transduction and glucoregulatory events in rat F<sub>1<\/sub> male offspring"],"prefix":"10.1002","volume":"39","author":[{"given":"Gokulapriya","family":"Rajagopal","sequence":"first","affiliation":[{"name":"Department of Endocrinology Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani  Chennai 600 113 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi Sankar","family":"Bhaskaran","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani  Chennai 600 113 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0155-3259","authenticated-orcid":false,"given":"Balasubramanian","family":"Karundevi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani  Chennai 600 113 India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.6.1319"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81896-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126403"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2014.09.005"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1415"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2017.09.009"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1104052"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1996.270.4.E667"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijheh.2013.01.006"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2009.02.008"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.16.8197"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-9936(03)01201-9"},{"issue":"119","key":"e_1_2_8_14_1","article-title":"Insulin regulates expression of metabolic genes through divergent signaling pathways","volume":"10","author":"Hall R.","year":"1999","journal-title":"Journal of Basic and Clinical Physiology and Pharmacology"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(57)03345-5"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/oem.2004.017590"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijheh.2007.07.011"},{"issue":"6","key":"e_1_2_8_18_1","article-title":"Gender and racial\/ethnic differences in the associations of urinary phthalate metabolites with markers of diabetes risk: national health and nutrition examination survey 2001\u20132008","volume":"13","author":"Huang T.","year":"2014","journal-title":"Environmental Health"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1104717"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12940-016-0136-x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2017.16"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.70.2.1238-1241.2004"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2015.06.019"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.2005.00607.x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2011.01.013"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-013-0432-6"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cccn.2005.05.003"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(62)05196-4"},{"key":"e_1_2_8_29_1","doi-asserted-by":"crossref","unstructured":"Leng S. 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