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It can easily cross the placenta and enter breast milk and then it is rapidly absorbed by offspring. Since it is generally accepted that individuals are more sensitive to chemical exposure during vital developmental periods, we investigated whether DEHP exposure during lactation affects cardiac insulin signaling and glucose homeostasis in the F<jats:sub>1<\/jats:sub> male rat offspring at postnatal day 22 (PND22). Lactating Wistar rats were administered with DEHP (1, 10, and 100\u2009mg\/kg\/d) or olive oil from lactation day 1 to 21 by oral gavage. All the male pups were perfused and killed on PND22. On the day before the killing, they were kept for fasting overnight and blood was collected. The cardiac muscle was dissected out, washed in ice\u2010cold physiological saline repeatedly and used for the assay of various parameters. DEHP\u2010exposed offspring had significantly lower body weight than the control. DEHP\u2010exposed offspring showed elevated blood glucose, decreased <jats:sup>14<\/jats:sup>C\u20102\u2010deoxyglucose uptake and <jats:sup>14<\/jats:sup>C\u2010glucose oxidation in cardiac muscle at PND22. The concentration of upstream insulin signaling molecules such as insulin receptor subunit \u03b2 (InsR\u03b2) and insulin\u00a0receptor substrate 1 (IRS1) were downregulated in DEHP\u2010exposed offspring. However, no significant alterations were observed in protein kinase B (Akt) and Akt substrate of 160\u2009kDa (AS160). Surprisingly, phosphorylation of IRS1\n<jats:sup>Tyr632<\/jats:sup> and Akt\n<jats:sup>Ser473<\/jats:sup> were diminished. Low levels of glucose transporter type 4 (GLUT4) protein and increased GLUT4\n<jats:sup>Ser488<\/jats:sup> phosphorylation which decreases its intrinsic activity and translocation towards plasma membrane were also recorded. Lactational DEHP exposure predisposes F\n<jats:sub>1<\/jats:sub> male offspring to cardiac glucometabolic disorders at PND22, which may impair cardiac function.<\/jats:p>","DOI":"10.1002\/jcb.27866","type":"journal-article","created":{"date-parts":[[2018,10,26]],"date-time":"2018-10-26T03:15:21Z","timestamp":1540523721000},"page":"5802-5812","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Postnatal exposure to di\u2010(2\u2010ethylhexyl)phthalate alters cardiac insulin signaling molecules and GLUT4<sup><b>Ser488<\/b><\/sup> phosphorylation in male rat offspring"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-3507","authenticated-orcid":false,"given":"Rajesh","family":"Parsanathan","sequence":"first","affiliation":[{"name":"Department of Endocrinology Dr ALM Post Graduate Institute of Basic Medical Sciences University of Madras Taramani 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