{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:25:14Z","timestamp":1791599114449,"version":"4.3.4"},"reference-count":48,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:p> Endocrine pancreas from pregnant rats undergoes several adaptations that comprise increase in \u03b2-cell number, mass and insulin secretion, and reduction of apoptosis. Lactogens are the main hormones that account for these changes. Maternal pancreas, however, returns to a nonpregnant state just after the delivery. The precise mechanism by which this reversal occurs is not settled but, in spite of high lactogen levels, a transient increase in apoptosis was already reported as early as the 3rd day of lactation (L3). Our results revealed that maternal islets displayed a transient increase in DNA fragmentation at L3, in parallel with decreased RAC-alpha serine\/threonine-protein kinase (AKT) phosphorylation (pAKT), a known prosurvival kinase. Wortmannin completely abolished the prosurvival action of prolactin (PRL) in cultured islets. Decreased pAKT in L3-islets correlated with increased Tribble 3 (TRB3) expression, a pseudokinase inhibitor of AKT. PERK and eIF2\u03b1 phosphorylation transiently increased in islets from rats at the first day after delivery, followed by an increase in immunoglobulin heavy chain-binding protein (BiP), activating transcription factor 4 (ATF4), and C\/EBP homologous protein (CHOP) in islets from L3 rats. Chromatin immunoprecipitation (ChIP) and Re-ChIP experiments further confirmed increased binding of the heterodimer ATF4\/CHOP to the TRB3 promoter in L3 islets. Treatment with PBA, a chemical chaperone that inhibits UPR, restored pAKT levels and inhibited the increase in apoptosis found in L3. Moreover, PBA reduced CHOP and TRB3 levels in \u03b2-cell from L3 rats. Altogether, our study collects compelling evidence that UPR underlies the physiological and transient increase in \u03b2-cell apoptosis after delivery. The UPR is likely to counteract prosurvival actions of PRL by reducing pAKT through ATF4\/CHOP-induced TRB3 expression. <\/jats:p>","DOI":"10.1152\/ajpregu.00169.2010","type":"journal-article","created":{"date-parts":[[2010,11,11]],"date-time":"2010-11-11T03:11:17Z","timestamp":1289445077000},"page":"R92-R100","source":"Crossref","is-referenced-by-count":76,"title":["UPR induces transient burst of apoptosis in islets of early lactating rats through reduced AKT phosphorylation via ATF4\/CHOP stimulation of TRB3 expression"],"prefix":"10.1152","volume":"300","author":[{"given":"Carla R.","family":"Bromati","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilo","family":"Lellis-Santos","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana S.","family":"Yamanaka","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiane C. A.","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Leonelli","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana C.","family":"Caperuto","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Federal University of Sao Paulo, Diadema, Brazil; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Gorj\u00e3o","sequence":"additional","affiliation":[{"name":"Institute of Physical Activity Sciences and Sports, Cruzeiro do Sul University, Sao Paulo, Brazil; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana R.","family":"Leite","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel F.","family":"Anh\u00ea","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana","family":"Bordin","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.05547"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2003-41303"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2010.01.003"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-07-0010"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.06.002"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1042\/bj1660501"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2004.04.001"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/BF00207273"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1210\/endo.132.2.8425500"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2008.02.019"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.026062"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/11047"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1677\/jme.1.01655"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1210\/er.2007-0015"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.080238"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2337\/db08-0080"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-1003"},{"key":"B18","first-page":"31","volume":"9","author":"Hubinont CJ","year":"1987","journal-title":"J Dev Physiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-1494"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1410419"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0478"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-006-0590-z"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2337\/diab.35.2.172"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200408003"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-09-0356"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.153.5.1011"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600596"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1126\/science.1128294"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2337\/db06-1253"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1506-5"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-08-0331"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2009.11.001"},{"key":"B32a","first-page":"345","volume-title":"Translational Control in Biology and Medicine","author":"Ron D","year":"2007"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2199"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1210\/endo.136.12.7588296"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1210\/er.2007-0039"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/nm1259"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.042"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1172\/JCI34587"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-979040"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200311055"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/nm1001-1133"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1379\/1466-1268(1996)001<0109:IOMACC>2.3.CO;2"},{"key":"B43","first-page":"665","volume":"5","author":"Whitacre CM","year":"1999","journal-title":"Clin Cancer Res"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208756200"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.3.478"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(03)00022-4"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00611-0"}],"container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpregu.00169.2010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T16:35:01Z","timestamp":1567960501000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpregu.00169.2010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,1]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,1]]}},"alternative-id":["10.1152\/ajpregu.00169.2010"],"URL":"https:\/\/doi.org\/10.1152\/ajpregu.00169.2010","relation":{},"ISSN":["0363-6119","1522-1490"],"issn-type":[{"value":"0363-6119","type":"print"},{"value":"1522-1490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,1]]}}}