{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:22:00Z","timestamp":1766049720089,"version":"build-2065373602"},"reference-count":48,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2015\/12611\u20100","2016\/23140\u20100","2019\/10543\u20108"],"award-info":[{"award-number":["2015\/12611\u20100","2016\/23140\u20100","2019\/10543\u20108"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005667","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa e Inova\u00e7\u00e3o do Estado de Santa Catarina","doi-asserted-by":"publisher","award":["2017TR1760"],"award-info":[{"award-number":["2017TR1760"]}],"id":[{"id":"10.13039\/501100005667","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["420602\/2018\u20106","304388\/2020\u20103"],"award-info":[{"award-number":["420602\/2018\u20106","304388\/2020\u20103"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Since prenatal glucocorticoids (GC) excess increases the risk of metabolic dysfunctions in the offspring and its effect on \u03b2\u2010cell recovery capacity remains unknown we investigated these aspects in offspring from mice treated with dexamethasone (DEX) in the late pregnancy. Half of the pups were treated with streptozotocin (STZ) on the sixth postnatal day (PN). Functional and molecular analyses were performed in male offspring on PN25 and PN225. Prenatal DEX treatment resulted in low birth weight. At PN25, both the STZ\u2010treated offspring developed hyperglycemia and had lower \u03b2\u2010cell mass, in parallel with higher \u03b1\u2010cell mass and glucose intolerance, with no impact of prenatal DEX on such parameters. At PN225, the \u03b2\u2010cell mass was partially recovered in the STZ\u2010treated mice, but they remained glucose\u2010intolerant, irrespective of being insulin sensitive. Prenatal exposition to DEX predisposed adult offspring to sustained hyperglycemia and perturbed islet function (lower insulin and higher glucagon response to glucose) in parallel with exacerbated glucose intolerance. \u03b2\u2010cell\u2010specific knockdown of the Hnf4\u03b1 in mice from the DS group resulted in exacerbated glucose intolerance. We conclude that high GC exposure during the prenatal period exacerbates the metabolic dysfunctions in adult life of mice exposed to STZ early in life, resulting in a lesser ability to recover the islets\u2019 function over time. This study alerts to the importance of proper management of exogenous GCs during pregnancy and a healthy postnatal lifestyle since the combination of adverse factors during the prenatal and postnatal period accentuates the predisposition to metabolic disorders in adult life.<\/jats:p>","DOI":"10.1096\/fj.202100841r","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T20:00:38Z","timestamp":1627588838000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Excess of glucocorticoids during late gestation impairs the recovery of offspring\u2019s \u03b2\u2010cell function after a postnatal injury"],"prefix":"10.1096","volume":"35","author":[{"given":"Cristiane","family":"dos Santos","sequence":"first","affiliation":[{"name":"Laboratory of Endocrine Pancreas and Metabolism \u2013 LAPEM, Department of Structural and Functional Biology, Institute of Biology Campinas State University \u2012 UNICAMP Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Rafacho","sequence":"additional","affiliation":[{"name":"Laboratory of Investigation in Chronic Diseases \u2013 LIDoC, Department of Physiological Sciences, Center of Biological Sciences Federal University of Santa Catarina \u2012 UFSC Florian\u00f3polis Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra Mara","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrine Pancreas and Metabolism \u2013 LAPEM, Department of Structural and Functional Biology, Institute of Biology Campinas State University \u2012 UNICAMP Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean Franciesco","family":"Vettorazzi","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrine Pancreas and Metabolism \u2013 LAPEM, Department of Structural and Functional Biology, Institute of Biology Campinas State University \u2012 UNICAMP Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thiago","family":"dos Reis Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrine Pancreas and Metabolism \u2013 LAPEM, Department of Structural and Functional Biology, Institute of Biology Campinas State University \u2012 UNICAMP Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana","family":"Mateus Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrine Pancreas and Metabolism \u2013 LAPEM, Department of Structural and Functional Biology, Institute of Biology Campinas State University \u2012 UNICAMP Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Ruhrmann","sequence":"additional","affiliation":[{"name":"Epigenetics and Diabetes Unit, Department of Clinical Sciences Malm\u00f6, Lund University Diabetes Center Scania University Hospital Malm\u00f6 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Bacos","sequence":"additional","affiliation":[{"name":"Epigenetics and Diabetes Unit, Department of Clinical Sciences Malm\u00f6, Lund University Diabetes Center Scania University Hospital Malm\u00f6 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Ling","sequence":"additional","affiliation":[{"name":"Epigenetics and Diabetes Unit, Department of Clinical Sciences Malm\u00f6, Lund University Diabetes Center Scania University Hospital Malm\u00f6 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ant\u00f4nio Carlos","family":"Boschero","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrine Pancreas and Metabolism \u2013 LAPEM, Department of Structural and Functional Biology, Institute of Biology Campinas State University \u2012 UNICAMP Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9135-7184","authenticated-orcid":false,"given":"Gustavo","family":"Jorge dos Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Investigation in Chronic Diseases \u2013 LIDoC, Department of Physiological Sciences, Center of Biological Sciences Federal University of Santa Catarina \u2012 UFSC Florian\u00f3polis Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.141.6.7567"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.130.3.1459"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.23.11.889"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.12.015"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32959"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00418372"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.11.8501"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.3.608"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13633"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08894"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.12.030"},{"key":"e_1_2_8_13_1","first-page":"91","article-title":"Studies on the diabetogenic action of streptozotocin (NSC\u201037917)","volume":"29","author":"Rakieten N","year":"1963","journal-title":"Cancer Chemother Rep"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11030605"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2018100882"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2019.107843"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197608122950701"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2014.73"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(89)90710-1"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003081-200606000-00009"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-09-0390"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00137.2004"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.50.4.515"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1567"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-10642-1"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30982"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgz145"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/983453"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0396"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2020.108572"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.482"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11089"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-6383(99)80009-5"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.2001.281.3.E592"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.13441"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.151U049"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2006.151"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20030278"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1159\/000439488"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4239-x"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.08.007"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-010-1898-2"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2019.09.010"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00403301"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051277"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-19-0009"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.2337\/db20-0009"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1019007108"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.47.1.50"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202100841R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202100841R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202100841R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:58:55Z","timestamp":1761699535000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202100841R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,29]]},"references-count":48,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1096\/fj.202100841R"],"URL":"https:\/\/doi.org\/10.1096\/fj.202100841r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"type":"print","value":"0892-6638"},{"type":"electronic","value":"1530-6860"}],"subject":[],"published":{"date-parts":[[2021,7,29]]},"assertion":[{"value":"2021-05-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e21828"}}