{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:24:54Z","timestamp":1788866694380,"version":"build-2803163510"},"reference-count":77,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T00:00:00Z","timestamp":1495756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["RO1DK084842"],"award-info":[{"award-number":["RO1DK084842"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["RO1DK088139"],"award-info":[{"award-number":["RO1DK088139"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Placental insufficiency and intrauterine growth restriction (IUGR) of the fetus affects approximately 8% of all pregnancies and is associated with short\u2010 and long\u2010term disturbances in metabolism. In pregnant sheep, experimental models with a small, defective placenta that restricts delivery of nutrients and oxygen to the fetus result in IUGR. Low blood oxygen concentrations increase fetal plasma catecholamine concentrations, which lower fetal insulin concentrations. All of these observations in sheep models with placental insufficiency are consistent with cases of human IUGR. We propose that sustained high catecholamine concentrations observed in the IUGR fetus produce developmental adaptations in pancreatic \u03b2\u2010cells that impair fetal insulin secretion. Experimental evidence supporting this hypothesis shows that chronic elevation in circulating catecholamines in IUGR fetuses persistently inhibits insulin concentrations and secretion. Elevated catecholamines also allow for maintenance of a normal fetal basal metabolic rate despite low fetal insulin and glucose concentrations while suppressing fetal growth. Importantly, a compensatory augmentation in insulin secretion occurs following inhibition or cessation of catecholamine signalling in IUGR fetuses. This finding has been replicated in normally grown sheep fetuses following a 7\u2010day noradrenaline (norepinephrine) infusion. Together, these programmed effects will potentially create an imbalance between insulin secretion and insulin\u2010stimulated glucose utilization in the neonate which probably explains the transient hyperinsulinism and hypoglycaemia in some IUGR infants.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp12280-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1113\/jp273324","type":"journal-article","created":{"date-parts":[[2017,2,14]],"date-time":"2017-02-14T08:52:52Z","timestamp":1487062372000},"page":"5103-5113","source":"Crossref","is-referenced-by-count":70,"title":["Fetal adaptations in insulin secretion result from high catecholamines during placental insufficiency"],"prefix":"10.1113","volume":"595","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5851-0439","authenticated-orcid":false,"given":"Sean W.","family":"Limesand","sequence":"first","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences University of Arizona  Tucson AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Rozance","sequence":"additional","affiliation":[{"name":"Perinatal Research Center University of Colorado School of Medicine  Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,5,26]]},"reference":[{"key":"e_1_2_3_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00519.x"},{"key":"e_1_2_3_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2012-302880"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00399095"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1998.274.6.R1536"},{"key":"e_1_2_3_6_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.111.4.804"},{"key":"e_1_2_3_7_1","first-page":"17","article-title":"Some aspects of placental function in chronically heat\u2010stressed ewes","volume":"9","author":"Bell AW","year":"1987","journal-title":"J\u00a0Dev Physiol"},{"key":"e_1_2_3_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00484.2016"},{"key":"e_1_2_3_9_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.2.385"},{"key":"e_1_2_3_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016-1328"},{"key":"e_1_2_3_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00517.2013"},{"key":"e_1_2_3_12_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-16-0445"},{"key":"e_1_2_3_13_1","doi-asserted-by":"publisher","DOI":"10.1258\/ebm.2012.011375"},{"key":"e_1_2_3_14_1","first-page":"R1340","article-title":"Fetal adrenal medulla catecholamine response to hypoxia\u2010direct and neural components","volume":"258","author":"Cheung CY","year":"1990","journal-title":"Am J Physiol"},{"key":"e_1_2_3_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1991.261.1.E95"},{"key":"e_1_2_3_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu7010500"},{"key":"e_1_2_3_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-0653"},{"key":"e_1_2_3_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00259.2004"},{"key":"e_1_2_3_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1990.259.4.E506"},{"key":"e_1_2_3_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(89)90167-1"},{"key":"e_1_2_3_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9136(199803)15:3<220::AID-DIA544>3.0.CO;2-O"},{"key":"e_1_2_3_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2006.05.039"},{"key":"e_1_2_3_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0233"},{"key":"e_1_2_3_24_1","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-09-0399"},{"key":"e_1_2_3_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-3782(90)90124-2"},{"key":"e_1_2_3_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.303.6809.1019"},{"key":"e_1_2_3_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwk071"},{"key":"e_1_2_3_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/apa.13413"},{"key":"e_1_2_3_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2005.10.002"},{"key":"e_1_2_3_30_1","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.2337\/diab.42.11.1621","article-title":"Hypoxia\u2010induced sympathetic inhibition of the fetal plasma insulin response to hyperglycemia","volume":"42","author":"Jackson BT","year":"1993","journal-title":"Diabetes"},{"key":"e_1_2_3_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2000.279.6.R2179"},{"key":"e_1_2_3_32_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.4.1271"},{"key":"e_1_2_3_33_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-2360"},{"key":"e_1_2_3_34_1","first-page":"77","article-title":"Studies on experimental growth retardation in sheep. Plasma catecholamines in fetuses with small placenta","volume":"5","author":"Jones CT","year":"1983","journal-title":"J\u00a0Dev Physiol"},{"key":"e_1_2_3_35_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016-1901"},{"key":"e_1_2_3_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00413.2012"},{"key":"e_1_2_3_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00494.2009"},{"key":"e_1_2_3_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2003.00095.x"},{"key":"e_1_2_3_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90832.2008"},{"key":"e_1_2_3_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00435.2012"},{"key":"e_1_2_3_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00459.2007"},{"key":"e_1_2_3_42_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0900"},{"key":"e_1_2_3_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00487.2014"},{"key":"e_1_2_3_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2010.02737.x"},{"key":"e_1_2_3_45_1","doi-asserted-by":"publisher","DOI":"10.1017\/S2040174413000093"},{"key":"e_1_2_3_46_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2015-1850"},{"key":"e_1_2_3_47_1","first-page":"64","article-title":"Fetal oxygenation in diabetic pregnancy. With special reference to maternal blood oxygen affinity and its effectors","volume":"33","author":"Madsen H","year":"1986","journal-title":"Dan Med Bull"},{"key":"e_1_2_3_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-0036-z"},{"key":"e_1_2_3_49_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1997.273.2.E336"},{"key":"e_1_2_3_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100337"},{"key":"e_1_2_3_51_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.156.10.999"},{"key":"e_1_2_3_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2016.11.1008"},{"key":"e_1_2_3_53_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199305000-00014"},{"key":"e_1_2_3_54_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-5491.2003.00871.x"},{"key":"e_1_2_3_55_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1004939"},{"key":"e_1_2_3_56_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.142141"},{"key":"e_1_2_3_57_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00706.2006"},{"key":"e_1_2_3_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00399954"},{"key":"e_1_2_3_59_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2008.02.002"},{"key":"e_1_2_3_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(86)90391-1"},{"key":"e_1_2_3_61_1","first-page":"379","article-title":"Studies on experimental growth retardation in sheep. The effect of removal of a endometrial caruncles on fetal size and metabolism","volume":"1","author":"Robinson JS","year":"1979","journal-title":"J\u00a0Dev Physiol"},{"key":"e_1_2_3_62_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1996.270.3.E491"},{"key":"e_1_2_3_63_1","doi-asserted-by":"publisher","DOI":"10.2337\/db14-0462"},{"key":"e_1_2_3_64_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00643.2005"},{"key":"e_1_2_3_65_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00265.2006"},{"key":"e_1_2_3_66_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199712000-00015"},{"key":"e_1_2_3_67_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-030031"},{"key":"e_1_2_3_68_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198003000-00005"},{"key":"e_1_2_3_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2015.02.045"},{"key":"e_1_2_3_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2010.05.005"},{"key":"e_1_2_3_71_1","doi-asserted-by":"publisher","DOI":"10.2337\/db11-1727"},{"key":"e_1_2_3_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2015.03.057"},{"key":"e_1_2_3_73_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1992.263.3.R578"},{"key":"e_1_2_3_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1977.tb12486.x"},{"key":"e_1_2_3_75_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.1995.tb00487.x"},{"key":"e_1_2_3_76_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.237347"},{"key":"e_1_2_3_77_1","first-page":"351","article-title":"The study of levels of norepinephrine and dopamine\u2010beta\u2010hydroxylase in patients with pregnancy\u2010induced hypertension","volume":"64","author":"Zhang W","year":"2001","journal-title":"Zhonghua Yi Xue Za Zhi (Taipei)"},{"key":"e_1_2_3_78_1","doi-asserted-by":"publisher","DOI":"10.2337\/db15-0494"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FJP273324","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP273324","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T20:41:59Z","timestamp":1696192919000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP273324"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,26]]},"references-count":77,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2017,8]]}},"alternative-id":["10.1113\/JP273324"],"URL":"https:\/\/doi.org\/10.1113\/jp273324","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,26]]}}}