{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T03:44:14Z","timestamp":1780717454271,"version":"3.54.1"},"reference-count":72,"publisher":"American Physiological Society","issue":"4","funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK140365"],"award-info":[{"award-number":["R01DK140365"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["Physiology"],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:p>\n                    Pancreatic \u03b2-cells couple nutrient and hormone sensing to insulin release. Prevailing models depict the \u03b2-cell as a homogeneous metabolic unit, overlooking specialized subcellular compartments like the primary cilium. Primary cilia are sensory organelles that function as critical signaling hubs in pancreatic \u03b2-cells. Disrupting primary cilia causes diabetes, but the underlying mechanisms remain unclear. In this review, we critically assess evidence supporting the cilium\u2019s role in \u03b2-cells, including functional studies that implicate cilia in the control of cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    dynamics and exocytosis, molecular studies that identify key hormone receptors on \u03b2-cell cilia, and genetic data linking cilia gene perturbations with diabetes in humans and rodents. We argue that the evidence for an acute function in stimulus-secretion coupling is insufficient and outline the missing links required to define the cilium\u2019s precise signaling role, focusing on how it might detect glucose and hormonal inputs, generate an outgoing signal, and relay this information to the cell body to control insulin secretion. Resolving these questions will not only clarify a fundamental aspect of \u03b2-cell biology but may reveal principles of subcellular signaling relevant to physiology and disease in other organ systems.\n                  <\/jats:p>","DOI":"10.1152\/physiol.00042.2025","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T15:50:47Z","timestamp":1766505047000},"page":"344-351","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Compartmentalized Nutrient and Hormone Sensing in \u03b2-Cells: the Role of Primary Cilia"],"prefix":"10.1152","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4397-8175","authenticated-orcid":false,"given":"Jing W.","family":"Hughes","sequence":"first","affiliation":[{"name":"Yale School of Medicine","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1599-9227","authenticated-orcid":false,"given":"Matthew J.","family":"Merrins","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00317-7"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.10.007"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112394"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.79422"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2337\/dbi23-0032"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100442"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.55013"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.264325"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-023-00698-5"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0116-4"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-023-00587-9"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00797-x"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6308"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12953-5"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2001936117"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3092"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00018.2024"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-018-0200-x"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.962933"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.16871020"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv447"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1113220108"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711027105"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.05.015"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.02.056"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06693-2"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.185116"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/srep45961"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-53348-5"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abq8486"},{"key":"B31","doi-asserted-by":"publisher","unstructured":"Dong X, Jo JH, Hughes J. Ultrastructure expansion microscopy of axonemal dynein in islet primary cilia (Preprint). bioRxiv 2024.09.06.611752, 2025. doi:10.1101\/2024.09.06.611752. 39282374","DOI":"10.1101\/2024.09.06.611752"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.262038"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1080\/19382014.2023.2252855"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.02.044"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0140378"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.50434"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.10.050"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.08.010"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E05-04-0347"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2640-16.2017"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.09.021"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00754-6"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.11.005"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1101\/gad.348261.121"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2023.110981"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69395"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-017-0020-9"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2013.203"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1126\/science.adp3989"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202108101"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/s44318-025-00383-7"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1966210"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E22-10-0473"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.11.036"},{"key":"B55","doi-asserted-by":"publisher","unstructured":"Ren H, Li Y, Xie B, Qian W, Yu Y, Chang T, Yang X, Sneppen K, Chen L, Tang C. \u03b4-\u03b1 cell-to-cell interactions modulate pancreatic islet Ca\n                      2+\n                      oscillation modes (Preprint). bioRxiv 2024.08.21.608986, 2024. doi:10.1101\/2024.08.21.608986.","DOI":"10.1101\/2024.08.21.608986"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1126\/science.2665080"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.123.6.1687"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90051-7"},{"key":"B59","doi-asserted-by":"publisher","unstructured":"Chang CH, Trinh VN, Lokesh NR, Montecinos CK, Pownall ME, Kalocsay M, Nachury MV. In situ proteomics unveils specialized domains for extrasynaptic signaling on neuronal cilia (Preprint). bioRxiv 2025.09.10.675452, 2025.\u2009doi:10.1101\/2025.09.10.675452.","DOI":"10.1101\/2025.09.10.675452"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2012.01.031"},{"key":"B61","doi-asserted-by":"publisher","unstructured":"Liu X, Gutierrez OT, Kaur G, Al-Issa Y, Baboo S, Diedrich JK, Cai E, Yates JR, Ge X. Proteomic profiling of primary cilia in the developing brain uncovers new regulators of cortical development (Preprint). bioRxiv 2025.05.03.652041, 2025. doi:10.1101\/2025.05.03.652041. 40654709.","DOI":"10.1101\/2025.05.03.652041"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.10.015"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.100992"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200504008"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-025-01594-6"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-022-00770-2"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.2337\/db24-1732-P"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-022-02886-4"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.002"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202154315"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.57907"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2019.01.054"}],"container-title":["Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/physiol.00042.2025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T13:50:28Z","timestamp":1780667428000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/physiol.00042.2025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":72,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,7,1]]}},"alternative-id":["10.1152\/physiol.00042.2025"],"URL":"https:\/\/doi.org\/10.1152\/physiol.00042.2025","relation":{},"ISSN":["1548-9213","1548-9221"],"issn-type":[{"value":"1548-9213","type":"print"},{"value":"1548-9221","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"assertion":[{"value":"2025-11-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-21","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}