{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:47:27Z","timestamp":1782452847364,"version":"3.54.5"},"reference-count":35,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T00:00:00Z","timestamp":1757116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100013111","name":"Tip-top Scientific and Technical Innovative Youth Talents of Guangdong Special Support Program","doi-asserted-by":"publisher","award":["2021TQ06N130"],"award-info":[{"award-number":["2021TQ06N130"]}],"id":[{"id":"10.13039\/501100013111","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Current research indicates that insulin secretion deficiency in \u03b2\u2010cells contributes to Type 2 diabetes mellitus (T2DM), which is associated with neuropeptide Y\n                    <jats:sub>1<\/jats:sub>\n                    receptor (Npy1r) overexpression from neuropeptide Y (NPY) system dysregulation. To date, limited literature has explored nobiletin (NOB) as a circadian modulator for restoring \u03b2\u2010cell function through Npy1r regulation. This study investigates NOB's stimulatory effects on insulin secretion via Npy1r and clock\u2010modulatory signaling to elucidate its underlying mechanism. The findings demonstrated that NOB ameliorated hyperglycemia and promoted insulin secretion in two distinct mouse models: T2DM induced by a high\u2010fat diet with low\u2010dose streptozotocin, and acute hyperglycemia triggered by NPY. Moreover, NOB reduced NPY family peptides in the serum and suppressed Npy1r overexpression in \u03b2\u2010cells. Comprehensive investigations revealed that NOB mitigated Npy1r\u2010mediated \u03b2\u2010cell dysfunction through activating clock\u2010modulatory signaling, evidenced by restored\n                    <jats:italic>Bmal1::Luc<\/jats:italic>\n                    bioluminescence rhythmicity in mouse insulinoma6 (MIN6) cells. Molecular docking confirmed a direct NOB\u2010Npy1r interaction, while mechanistic analyses demonstrated modulation of the retinoic acid\u2010related orphan receptors (RORs)\/Bmal1\u2010Yes\u2010associated protein (Yap) pathway via Yap suppression and Bmal1 activation, based on the interventions with palmitic acid, BMS 193885 (Npy1r antagonist), and NPY. Therefore, this study provides evidence that NOB can protect \u03b2\u2010cells from insulin secretion dysfunction by downregulating Npy1r expression and activating the RORs\/Bmal1\u2010Yap pathway.\n                  <\/jats:p>","DOI":"10.1002\/mnfr.70208","type":"journal-article","created":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T12:49:14Z","timestamp":1757162954000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nobiletin Alleviates Npy1r\u2010Mediated Insulin Secretion Deficiency of Islet \u03b2\u2010Cells via the Clock\u2010Modulatory Signaling"],"prefix":"10.1002","volume":"69","author":[{"given":"Qianru","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public Health Southern Medical University  Guangzhou Guangdong China"},{"name":"Department of Clinical Nutrition the Second School of Clinical Medicine Zhujiang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public Health Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enhui","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public Health Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism the Eighth Affiliated Hospital of Southern Medical University  Foshan Guangdong China"},{"name":"GuangDong Engineering Technology Research Center of Metabolic Disorders Interdisciplinary Precision Prevention and Digital Healthcare the Eighth Affiliated Hospital, Southern Medical University  Foshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijun","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public Health Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7127-8593","authenticated-orcid":false,"given":"Wenzhen","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public Health Southern Medical University  Guangzhou Guangdong China"},{"name":"Department of Clinical Nutrition the Second School of Clinical Medicine Zhujiang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2008.00939.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109119"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqab070"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.npep.2004.10.002"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202200289"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2FO01682F"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.7b03953"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.2c00148"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2010.01.034"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/13813455.2018.1555669"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20191099"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-023-01450-7"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.03.007"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/db20-0192"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac4250"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.150"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2021.08.001"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-022-00908-7"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202300529"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcd.2013.08.003"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00401058"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-127-1-126"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.1c00203"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.3c09344"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2022.120240"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.143079"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115886"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-0115(95)00114-5"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.94005"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00624-2"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202209120"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06860-x"},{"issue":"24","key":"e_1_2_10_35_1","article-title":"YAP\/TAZ, beta\u2010catenin, and TGFb pathway activation in medical plasma\u2010induced wound healing in diabetic mice","author":"Schmidt A.","year":"2024","journal-title":"Journal of Advanced Research"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25145-x"}],"container-title":["Molecular Nutrition &amp; Food Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mnfr.70208","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T14:34:03Z","timestamp":1765204443000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mnfr.70208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,6]]},"references-count":35,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/mnfr.70208"],"URL":"https:\/\/doi.org\/10.1002\/mnfr.70208","archive":["Portico"],"relation":{},"ISSN":["1613-4125","1613-4133"],"issn-type":[{"value":"1613-4125","type":"print"},{"value":"1613-4133","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,6]]},"assertion":[{"value":"2024-12-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70208"}}