{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T16:35:48Z","timestamp":1776357348525,"version":"3.51.2"},"reference-count":52,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2013,3,1]]},"abstract":"<jats:p> In pregnancy complicated by placental insufficiency (PI) and intrauterine growth restriction (IUGR), the fetus near term has reduced basal and glucose-stimulated insulin concentrations and reduced \u03b2-cell mass. To determine whether suppression of insulin concentrations and \u03b2-cell mass precedes reductions in fetal weight, which would implicate insulin deficiency as a cause of subsequent IUGR, we measured basal and glucose-stimulated insulin concentrations and pancreatic histology at 0.7 gestation in PI fetuses. Placental weights in the PI pregnancies were 40% lower than controls (265 \u00b1 26 vs. 442 \u00b1 41 g, P &lt; 0.05), but fetal weights were not different. At basal conditions blood oxygen content, plasma glucose concentrations, and plasma insulin concentrations were lower in PI fetuses compared with controls (2.5 \u00b1 0.3 vs. 3.5 \u00b1 0.3 mmol\/l oxygen, P &lt; 0.05; 1.11 \u00b1 0.09 vs. 1.44 \u00b1 0.12 mmol\/l glucose; 0.12 \u00b1 0.01 vs. 0.27 \u00b1 0.02 ng\/ml insulin; P &lt; 0.05). During a steady-state hyperglycemic clamp (\u223c2.5 \u00b1 0.1 mmol\/l), glucose-stimulated insulin concentrations were lower in PI fetuses than controls (0.28 \u00b1 0.02 vs. 0.55 \u00b1 0.04 ng\/ml; P &lt; 0.01). Plasma norepinephrine concentrations were 3.3-fold higher ( P &lt; 0.05) in PI fetuses (635 \u00b1 104 vs. 191 \u00b1 91 pg\/ml). Histological examination revealed less insulin area and lower \u03b2-cell mass and rates of mitosis. The pancreatic parenchyma was also less dense ( P &lt; 0.01) in PI fetuses, but no differences were found for pancreatic progenitor cells or other endocrine cell types. These findings show that hypoglycemia, hypoxemia, and hypercatecholaminemia are present and potentially contribute to lower insulin concentrations and \u03b2-cell mass due to slower proliferation rates in early third-trimester PI fetuses before discernible reductions in fetal weight. <\/jats:p>","DOI":"10.1152\/ajpendo.00435.2012","type":"journal-article","created":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T03:23:03Z","timestamp":1357010583000},"page":"E516-E523","source":"Crossref","is-referenced-by-count":56,"title":["Reductions in insulin concentrations and \u03b2-cell mass precede growth restriction in sheep fetuses with placental insufficiency"],"prefix":"10.1152","volume":"304","author":[{"given":"Sean W.","family":"Limesand","sequence":"first","affiliation":[{"name":"Department of Animal Sciences, University of Arizona, Tucson, Arizona; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"Rozance","sequence":"additional","affiliation":[{"name":"Section of Neonatology, Department of Pediatrics, University of Colorado-Denver, Aurora, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoni R.","family":"Macko","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, University of Arizona, Tucson, Arizona; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miranda J.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, University of Arizona, Tucson, Arizona; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy C.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, University of Arizona, Tucson, Arizona; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"William W.","family":"Hay","sequence":"additional","affiliation":[{"name":"Section of Neonatology, Department of Pediatrics, University of Colorado-Denver, Aurora, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1159\/000014000"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(95)91328-9"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2007.11.004"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1998.274.6.R1536"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2000.278.5.R1171"},{"key":"B6","first-page":"17","volume":"9","author":"Bell AW","year":"1987","journal-title":"J Dev Physiol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.2.385"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1258\/ebm.2012.011375"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1990.258.6.R1340"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-09-0072"},{"key":"B11","first-page":"569","volume-title":"Maternal-Fetal Medicine","author":"Creasy RK","year":"1999"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00259.2004"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(15)33298-1"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1990.tb02529.x"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1046\/j.0960-7692.2002.00627.x"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.1988.sp003231"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-11-0300"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00572.2010"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-09-0399"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1997.272.1.E68"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2003.09.045"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(89)90176-5"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051484"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00494.2009"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.026831"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00494.2004"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2003.08.012"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00459.2007"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0900"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1997.273.2.E336"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1991.261.3.R697"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1004939"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1989.257.2.R350"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.142141"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1987.252.4.E530"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(96)00062-1"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199303113281004"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2008.02.002"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2002.0792"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2001.0757"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2004.11.010"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e318189358c"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00265.2006"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(65)90761-0"},{"key":"B45","volume-title":"SAS\/STAT User's Guide","author":"SAS Institute","year":"1999"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1080\/00313020600696256"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.2337\/db11-1727"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-1789"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1992.263.3.R578"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1977.tb12486.x"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.082032"},{"key":"B52","author":"Yates DT","journal-title":"J Pregnancy."}],"container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpendo.00435.2012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T20:07:55Z","timestamp":1567973275000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpendo.00435.2012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,1]]},"references-count":52,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2013,3,1]]}},"alternative-id":["10.1152\/ajpendo.00435.2012"],"URL":"https:\/\/doi.org\/10.1152\/ajpendo.00435.2012","relation":{},"ISSN":["0193-1849","1522-1555"],"issn-type":[{"value":"0193-1849","type":"print"},{"value":"1522-1555","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,1]]}}}