{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:34:26Z","timestamp":1793054066806,"version":"4.5.0"},"reference-count":55,"publisher":"American Society for Clinical Investigation","issue":"20","license":[{"start":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T00:00:00Z","timestamp":1571270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Diabetes Research & Wellness Foundation","award":["SCA\/OF\/12\/13"],"award-info":[{"award-number":["SCA\/OF\/12\/13"]}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"crossref","award":["BB\/N00616X\/1"],"award-info":[{"award-number":["BB\/N00616X\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,17]]},"abstract":"<jats:p>During pregnancy the maternal pancreatic islets of Langerhans undergo adaptive changes to compensate for gestational insulin resistance. Kisspeptin has been shown to stimulate insulin release, through its receptor, GPR54. The placenta releases high levels of kisspeptin into the maternal circulation, suggesting a role in modulating the islet adaptation to pregnancy. In the present study we show that pharmacological blockade of endogenous kisspeptin in pregnant mice resulted in impaired glucose homeostasis. This glucose intolerance was due to a reduced insulin response to glucose as opposed to any effect on insulin sensitivity. A \u03b2 cell\u2013specific GPR54-knockdown mouse line was found to exhibit glucose intolerance during pregnancy, with no phenotype observed outside of pregnancy. Furthermore, in pregnant women circulating kisspeptin levels significantly correlated with insulin responses to oral glucose challenge and were significantly lower in women with gestational diabetes (GDM) compared with those without GDM. Thus, kisspeptin represents a placental signal that plays a physiological role in the islet adaptation to pregnancy, maintaining maternal glucose homeostasis by acting through the \u03b2 cell GPR54 receptor. Our data suggest reduced placental kisspeptin production, with consequent impaired kisspeptin-dependent \u03b2 cell compensation, may be a factor in the development of GDM in humans.<\/jats:p>","DOI":"10.1172\/jci.insight.124540","type":"journal-article","created":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T11:04:18Z","timestamp":1571223858000},"source":"Crossref","is-referenced-by-count":40,"title":["A role for placental kisspeptin in \u03b2 cell adaptation to pregnancy"],"prefix":"10.1172","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1169-9369","authenticated-orcid":true,"given":"James E.","family":"Bowe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4637-3879","authenticated-orcid":true,"given":"Thomas G.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharine F.","family":"Hunt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorna I.F.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sian J.S.","family":"Simpson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie A.","family":"Amiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2019,10,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1834399100"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa035322"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/35079135"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-006-0343-z"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2828-2"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.4161\/isl.18261"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1283-1"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0113020"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1268458"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13460"},{"issue":"2","key":"B11","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1677\/JOE-07-0454","article-title":"Kisspeptin-13 inhibits insulin secretion without affecting glucagon or somatostatin release: study in the perfused rat pancreas","volume":"196","author":"Silvestre","year":"2008","journal-title":"J Endocrinol"},{"issue":"Suppl 4","key":"B12","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/j.1463-1326.2009.01116.x","article-title":"Inhibitory effect of kisspeptins on insulin secretion from isolated mouse islets","volume":"11","author":"Vikman","year":"2009","journal-title":"Diabetes Obes Metab"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.03.005"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1172\/JCI71075"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016-1501"},{"key":"B16","doi-asserted-by":"crossref","DOI":"10.1016\/j.mce.2019.110559","article-title":"Cre\/lox generation of a novel whole-body Kiss1r KO mouse line recapitulates a hypogonadal, obese, and metabolically-impaired phenotype","volume":"498","author":"Tolson","year":"2019","journal-title":"Mol Cell Endocrinol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00555.2005"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2014.10.016"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2013.04.012"},{"key":"B20","doi-asserted-by":"crossref","DOI":"10.1186\/s12958-015-0083-3","article-title":"Regulation of kisspeptin and gonadotropin-releasing hormone expression in rat placenta: study using primary cultures of rat placental cells","volume":"13","author":"Oride","year":"2015","journal-title":"Reprod Biol Endocrinol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-009-9273-0"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0201"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-07-0043"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021235"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1530\/REP-09-0026"},{"issue":"7","key":"B27","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/35080570","article-title":"Placental development: lessons from mouse mutants","volume":"2","author":"Rossant","year":"2001","journal-title":"Nat Rev Genet"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.2337\/db10-1149"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20672"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.12863"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2337\/db15-0272"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.12.005"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2173"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1210\/er.2012-1055"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.07.015"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2018.08.004"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.2337\/db15-1527"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-010-1809-6"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.04.008"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3109\/07435800.2011.639319"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-011-2061-0"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2011.04317.x"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0707943"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2008.05.006"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0179834"},{"issue":"Pt 8","key":"B46","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1242\/jcs.00971","article-title":"Kisspeptin-10, a KiSS-1\/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts","volume":"117","author":"Bilban","year":"2004","journal-title":"J Cell Sci"},{"key":"B47","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2018.00184","article-title":"The emerging role(s) for kisspeptin in metabolism in mammals","volume":"9","author":"Wolfe","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1159\/000487357"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1260"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.4161\/isl.27685"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.09.044"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-1848"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2007.093005"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.21.12.2191"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.2337\/dc10-0646"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/124540\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:22:34Z","timestamp":1779193354000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/124540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,17]]},"references-count":55,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2019,10,17]]},"published-print":{"date-parts":[[2019,10,17]]}},"alternative-id":["10.1172\/jci.insight.124540"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.124540","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,17]]},"article-number":"e124540"}}