{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:43:56Z","timestamp":1790311436676,"version":"4.1.0"},"reference-count":108,"publisher":"National Academy of Sciences","issue":"45","license":[{"start":{"date-parts":[[2016,4,22]],"date-time":"2016-04-22T00:00:00Z","timestamp":1461283200000},"content-version":"vor","delay-in-days":183,"URL":"http:\/\/www.pnas.org\/site\/misc\/userlicense.xhtml"}],"funder":[{"DOI":"10.13039\/501100001870","name":"Foundation For Polish Science","doi-asserted-by":"publisher","award":["TEAM\/2020-5\/2"],"award-info":[{"award-number":["TEAM\/2020-5\/2"]}],"id":[{"id":"10.13039\/501100001870","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001870","name":"Foundation For Polish Science","doi-asserted-by":"publisher","award":["MPD\/2009\/4"],"award-info":[{"award-number":["MPD\/2009\/4"]}],"id":[{"id":"10.13039\/501100001870","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"HHS | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA023214"],"award-info":[{"award-number":["DA023214"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"HHS | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA011322"],"award-info":[{"award-number":["DA011322"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"HHS | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA021696"],"award-info":[{"award-number":["DA021696"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2013-3080"],"award-info":[{"award-number":["2013-3080"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2012-2273"],"award-info":[{"award-number":["2012-2273"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","award":["NNF15OC0015964"],"award-info":[{"award-number":["NNF15OC0015964"]}],"id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2015,11,10]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Glucagon and insulin are produced in distinct cell populations within pancreatic Langerhans islets, where intercellular interactions control their production and release. Modifications to the microstructure of pancreatic islets are implicated in disease pathogenesis, but the developmental rules underlying cell commitment and segregation are incompletely understood. We show that endocannabinoids (\u03c9-6) via CB\n                    <jats:sub>1<\/jats:sub>\n                    cannabinoid receptors and endovanilloid ligands via transient receptor potential cation channel subfamily V member 1, as well as dietary \u03c9-3 polyunsaturated fatty acids, affect the cellular organization of pancreatic islets during organ development. Thus, lipid signaling emerges as a key determinant of tissue organization and can program hormone secretion for life.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1519040112","type":"journal-article","created":{"date-parts":[[2015,10,22]],"date-time":"2015-10-22T23:13:46Z","timestamp":1445555626000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":58,"title":["Fetal endocannabinoids orchestrate the organization of pancreatic islet microarchitecture"],"prefix":"10.1073","volume":"112","author":[{"given":"Katarzyna","family":"Malenczyk","sequence":"first","affiliation":[{"name":"Division of Molecular Neurobiology, Department of Medical Biochemistry &amp; Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden;"},{"name":"Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland;"},{"name":"Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, A-1090 Vienna, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Keimpema","sequence":"additional","affiliation":[{"name":"Division of Molecular Neurobiology, Department of Medical Biochemistry &amp; Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden;"},{"name":"Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, A-1090 Vienna, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Piscitelli","sequence":"additional","affiliation":[{"name":"Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, I-80078 Pozzuoli, Naples, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Calvigioni","sequence":"additional","affiliation":[{"name":"Division of Molecular Neurobiology, Department of Medical Biochemistry &amp; Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peyman","family":"Bj\u00f6rklund","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Uppsala University, SE-75185 Uppsala, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Mackie","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences, Gill Center for Neuroscience, Indiana University, Bloomington, IN 47405;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Di Marzo","sequence":"additional","affiliation":[{"name":"Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, I-80078 Pozzuoli, Naples, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas G. M.","family":"H\u00f6kfelt","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Karolinska Institutet, SE-17177 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Dobrzyn","sequence":"additional","affiliation":[{"name":"Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tibor","family":"Harkany","sequence":"additional","affiliation":[{"name":"Division of Molecular Neurobiology, Department of Medical Biochemistry &amp; Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden;"},{"name":"Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, A-1090 Vienna, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2015,10,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2006.11.006"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.478354"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01422.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20120447"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1159\/000339069"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-2679"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.215434"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-7075-8-93"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.2337\/db12-0901"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2006.12.004"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047704"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.05.002"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.181206"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2396(19990901)33:3<181::AID-SYN3>3.0.CO;2-R"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2013.08.007"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2002519"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2007.106"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.4161\/isl.2.3.11815"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510790103"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/346561a0"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/22761"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1406728111"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2126-10.2010"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2601"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306642200"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.4161\/isl.1.2.9480"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.12.002"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200210164"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5483-10.2011"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-09-307355"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2012.10.006"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2010.46"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2012.12.031"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80778-3"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-9-2"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1177\/153537020322801020"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v17.i40.4479"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.129"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm800978m"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910310104"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81279-9"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(91)90332-W"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0803272"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2616"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.4161\/isl.18915"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep06697"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.17.12.1498"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-1092"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0284"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-7075-8-51"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.3945\/jn.109.104844"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0802583"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2009.234"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/35048589"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1002\/wdev.44"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.4161\/isl.1.3.9967"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1209200"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42551"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3614"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1105"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.110.068304"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.051"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.043711"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2008.01682.x"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.3109\/01902148.2013.813610"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgr037"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.144.2.325"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.2337\/db13-1001"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3101-05.2006"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.105.015040"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00253809"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(75)92375-2"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006639107"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.53.082901.104057"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.23.7322"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001250100003"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M002436"},{"key":"e_1_3_3_78_2","first-page":"255","article-title":"Murine pancreatic islet isolation","volume":"2007","author":"Szot GL","year":"2007","unstructured":"GL Szot, P Koudria, JA Bluestone, Murine pancreatic islet isolation. J Vis Exp 2007, 255 (2007).","journal-title":"J Vis Exp"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5400.401"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5464.306"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-511X-2-5"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.079855"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.078980"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0054-06.2006"},{"key":"e_1_3_3_85_2","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/S0026-895X(25)10254-X","article-title":"Activation of the human peripheral cannabinoid receptor results in inhibition of adenylyl cyclase","volume":"48","author":"Slipetz DM","year":"1995","unstructured":"DM Slipetz, , Activation of the human peripheral cannabinoid receptor results in inhibition of adenylyl cyclase. Mol Pharmacol 48, 352\u2013361 (1995).","journal-title":"Mol Pharmacol"},{"key":"e_1_3_3_86_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr046"},{"key":"e_1_3_3_87_2","doi-asserted-by":"publisher","DOI":"10.2337\/db10-1239"},{"key":"e_1_3_3_88_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69035"},{"key":"e_1_3_3_89_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.153734"},{"key":"e_1_3_3_90_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2004.09.006"},{"key":"e_1_3_3_91_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2000.0787"},{"key":"e_1_3_3_92_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2003.11.005"},{"key":"e_1_3_3_93_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3265"},{"key":"e_1_3_3_94_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1247"},{"key":"e_1_3_3_95_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20102118"},{"key":"e_1_3_3_96_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2011.07.002"},{"key":"e_1_3_3_97_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2012.08.002"},{"key":"e_1_3_3_98_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12255"},{"key":"e_1_3_3_99_2","first-page":"1013","article-title":"Potential roles of GPR120 and its agonists in the management of diabetes","volume":"8","author":"Zhang D","year":"2014","unstructured":"D Zhang, PS Leung, Potential roles of GPR120 and its agonists in the management of diabetes. Drug Des Devel Ther 8, 1013\u20131027 (2014).","journal-title":"Drug Des Devel Ther"},{"key":"e_1_3_3_100_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3213-0"},{"key":"e_1_3_3_101_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)00773-X"},{"key":"e_1_3_3_102_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2008.01693.x"},{"key":"e_1_3_3_103_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200305129"},{"key":"e_1_3_3_104_2","doi-asserted-by":"publisher","DOI":"10.1038\/384083a0"},{"key":"e_1_3_3_105_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.152334899"},{"key":"e_1_3_3_106_2","doi-asserted-by":"publisher","DOI":"10.1038\/372686a0"},{"key":"e_1_3_3_107_2","first-page":"371","article-title":"Localization of glucagon in the alpha cells in the pancreatic islet by immunofluorescent technics","volume":"11","author":"Baum J","year":"1962","unstructured":"J Baum, Jr BE Simons, RH Unger, LL Madison, Localization of glucagon in the alpha cells in the pancreatic islet by immunofluorescent technics. Diabetes 11, 371\u2013374 (1962).","journal-title":"Diabetes"},{"key":"e_1_3_3_108_2","doi-asserted-by":"publisher","DOI":"10.3109\/10520295909114654"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1519040112","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1519040112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T23:19:40Z","timestamp":1748647180000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1519040112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,22]]},"references-count":108,"journal-issue":{"issue":"45","published-print":{"date-parts":[[2015,11,10]]}},"alternative-id":["10.1073\/pnas.1519040112"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1519040112","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,22]]},"assertion":[{"value":"2015-10-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}