{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T08:08:23Z","timestamp":1786781303483,"version":"build-2736575974"},"reference-count":50,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["Z210011"],"award-info":[{"award-number":["Z210011"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022TQ0182"],"award-info":[{"award-number":["2022TQ0182"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32371008"],"award-info":[{"award-number":["32371008"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31830038"],"award-info":[{"award-number":["31830038"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["iScience"],"published-print":{"date-parts":[[2025,5]]},"DOI":"10.1016\/j.isci.2025.112354","type":"journal-article","created":{"date-parts":[[2025,4,6]],"date-time":"2025-04-06T17:52:07Z","timestamp":1743961927000},"page":"112354","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synaptotagmin-7 deficit causes insulin hypoactivity and contributes to behavioral alterations in mice"],"prefix":"10.1016","volume":"28","author":[{"given":"Yao-Nan","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu-Wen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Yao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongye","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhikai","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen-Fang","family":"Sui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangli","family":"Mi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred H.","family":"Gage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.isci.2025.112354_bib1","doi-asserted-by":"crossref","first-page":"4392","DOI":"10.1073\/pnas.1918165117","article-title":"Synaptotagmin-7 is a key factor for bipolar-like behavioral abnormalities in mice","volume":"117","author":"Shen","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2025.112354_bib2","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1177\/070674370304800705","article-title":"Clinical features of bipolar disorder with and without comorbid diabetes mellitus","volume":"48","author":"Ruzickova","year":"2003","journal-title":"Can. J. Psychiatry."},{"key":"10.1016\/j.isci.2025.112354_bib3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/YCO.0000000000000215","article-title":"Bipolar disorders, type 2 diabetes mellitus, and the brain","volume":"29","author":"Hajek","year":"2016","journal-title":"Curr. Opin. Psychiatry"},{"key":"10.1016\/j.isci.2025.112354_bib4","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.dsx.2015.04.004","article-title":"Levels of triglycerides, cholesterol, LDL, HDL and glucose in patients with schizophrenia, unipolar depression and bipolar disorder","volume":"9","author":"Wysokinski","year":"2015","journal-title":"Diabetes Metabol. Syndr."},{"key":"10.1016\/j.isci.2025.112354_bib5","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jad.2016.12.059","article-title":"Medical comorbidity in bipolar disorder: The link with metabolic-inflammatory systems","volume":"211","author":"SayuriYamagata","year":"2017","journal-title":"J. Affect. Disord."},{"key":"10.1016\/j.isci.2025.112354_bib6","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1080\/10401230701653377","article-title":"Should Depressive Syndromes Be Reclassified as \"Metabolic Syndrome Type II","volume":"19","author":"McIntyre","year":"2007","journal-title":"Ann. Clin. Psychiatry."},{"key":"10.1016\/j.isci.2025.112354_bib7","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1586\/ern.10.185","article-title":"Insulin dysfunction and allostatic load in bipolar disorder","volume":"11","author":"Brietzke","year":"2011","journal-title":"Expert Rev. Neurother."},{"key":"10.1016\/j.isci.2025.112354_bib8","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.jad.2011.06.033","article-title":"Use of insulin sensitizers for the treatment of major depressive disorder: a pilot study of pioglitazone for major depression accompanied by abdominal obesity","volume":"136","author":"Kemp","year":"2012","journal-title":"J. Affect. Disord."},{"key":"10.1016\/j.isci.2025.112354_bib9","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s40263-014-0158-2","article-title":"PPAR-gamma agonism as a modulator of mood: proof-of-concept for pioglitazone in bipolar depression","volume":"28","author":"Kemp","year":"2014","journal-title":"CNS Drugs"},{"key":"10.1016\/j.isci.2025.112354_bib10","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1038\/npp.2012.58","article-title":"Pioglitazone adjunctive therapy for moderate-to-severe major depressive disorder: randomized double-blind placebo-controlled trial","volume":"37","author":"Sepanjnia","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.isci.2025.112354_bib11","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/da.22340","article-title":"Pioglitazone adjunctive therapy for depressive episode of bipolar disorder: a randomized, double-blind, placebo-controlled trial","volume":"32","author":"Zeinoddini","year":"2015","journal-title":"Depress. Anxiety"},{"key":"10.1016\/j.isci.2025.112354_bib12","doi-asserted-by":"crossref","DOI":"10.1038\/emm.2015.3","article-title":"Insulin resistance as a key link for the increased risk of cognitive impairment in the metabolic syndrome","volume":"47","author":"Kim","year":"2015","journal-title":"Exp. Mol. Med."},{"key":"10.1016\/j.isci.2025.112354_bib13","doi-asserted-by":"crossref","first-page":"13906","DOI":"10.1073\/pnas.1008598107","article-title":"Distinct roles for two synaptotagmin isoforms in synchronous and asynchronous transmitter release at zebrafish neuromuscular junction","volume":"107","author":"Wen","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2025.112354_bib14","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.neuron.2013.10.026","article-title":"Synaptotagmin-1 and synaptotagmin-7 trigger synchronous and asynchronous phases of neurotransmitter release","volume":"80","author":"Bacaj","year":"2013","journal-title":"Neuron"},{"key":"10.1016\/j.isci.2025.112354_bib15","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.01524","article-title":"Synaptotagmin 7 functions as a Ca2+-sensor for synaptic vesicle replenishment","volume":"3","author":"Liu","year":"2014","journal-title":"Elife"},{"key":"10.1016\/j.isci.2025.112354_bib16","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nature16507","article-title":"The calcium sensor synaptotagmin 7 is required for synaptic facilitation","volume":"529","author":"Jackman","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.isci.2025.112354_bib17","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/nature21720","article-title":"Postsynaptic synaptotagmins mediate AMPA receptor exocytosis during LTP","volume":"544","author":"Wu","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.isci.2025.112354_bib18","doi-asserted-by":"crossref","first-page":"3992","DOI":"10.1073\/pnas.0711700105","article-title":"Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice","volume":"105","author":"Gustavsson","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2025.112354_bib19","doi-asserted-by":"crossref","first-page":"36079","DOI":"10.1074\/jbc.M004284200","article-title":"Synaptotagmin III\/VII isoforms mediate Ca2+-induced insulin secretion in pancreatic islet beta -cells","volume":"275","author":"Gao","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.isci.2025.112354_bib20","doi-asserted-by":"crossref","first-page":"9996","DOI":"10.1073\/pnas.1513004112","article-title":"Synaptotagmin-7 phosphorylation mediates GLP-1-dependent potentiation of insulin secretion from beta-cells","volume":"112","author":"Wu","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2025.112354_bib21","doi-asserted-by":"crossref","first-page":"31438","DOI":"10.1073\/pnas.2016416117","article-title":"Synaptotagmin-7 deficiency induces mania-like behavioral abnormalities through attenuating GluN2B activity","volume":"117","author":"Wang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2025.112354_bib22","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.neuron.2017.06.044","article-title":"Initiation of Behavioral Response to Antidepressants by Cholecystokinin Neurons of the Dentate Gyrus","volume":"95","author":"Medrihan","year":"2017","journal-title":"Neuron"},{"key":"10.1016\/j.isci.2025.112354_bib23","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ejphar.2004.02.045","article-title":"Insulin and the insulin receptor in experimental models of learning and memory","volume":"490","author":"Zhao","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.isci.2025.112354_bib24","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/emmm.201100177","article-title":"Insulin biosynthesis in neuronal progenitors derived from adult hippocampus and the olfactory bulb","volume":"3","author":"Kuwabara","year":"2011","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.isci.2025.112354_bib25","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1126\/science.1190287","article-title":"mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists","volume":"329","author":"Li","year":"2010","journal-title":"Science"},{"key":"10.1016\/j.isci.2025.112354_bib26","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nature10130","article-title":"NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses","volume":"475","author":"Autry","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.isci.2025.112354_bib27","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nature15526","article-title":"Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder","volume":"527","author":"Mertens","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.isci.2025.112354_bib28","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/s41467-017-00561-0","article-title":"Glycoprotein 2 is a specific cell surface marker of human pancreatic progenitors","volume":"8","author":"Cogger","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.isci.2025.112354_bib29","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1192\/bjp.bp.114.152850","article-title":"Insulin resistance and outcome in bipolar disorder","volume":"206","author":"Calkin","year":"2015","journal-title":"Br. J. Psychiatry"},{"key":"10.1016\/j.isci.2025.112354_bib30","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1111\/j.1399-5618.2005.00182.x","article-title":"Clinical correlates of current level of functioning in primary care-treated bipolar patients","volume":"7","author":"Hajek","year":"2005","journal-title":"Bipolar Disord."},{"key":"10.1016\/j.isci.2025.112354_bib31","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1176\/ajp.156.9.1417","article-title":"Elevated frequency of diabetes mellitus in hospitalized manic-depressive patients","volume":"156","author":"Cassidy","year":"1999","journal-title":"Am. J. Psychiatry"},{"key":"10.1016\/j.isci.2025.112354_bib32","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0165-0327(01)00456-6","article-title":"Increased prevalence of type 2 diabetes mellitus among psychiatric inpatients with bipolar I affective and schizoaffective disorders independent of psychotropic drug use","volume":"70","author":"Regenold","year":"2002","journal-title":"J. Affect. Disord."},{"key":"10.1016\/j.isci.2025.112354_bib33","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3109\/07853890.2012.687835","article-title":"The relationship between bipolar disorder and type 2 diabetes: more than just co-morbid disorders","volume":"45","author":"Calkin","year":"2013","journal-title":"Ann. Med."},{"key":"10.1016\/j.isci.2025.112354_bib34","doi-asserted-by":"crossref","first-page":"3463","DOI":"10.1073\/pnas.1500877112","article-title":"Insulin resistance in brain alters dopamine turnover and causes behavioral disorders","volume":"112","author":"Kleinridders","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2025.112354_bib35","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1158\/1078-0432.CCR-08-0801","article-title":"BMS-536924 reverses IGF-IR-induced transformation of mammary epithelial cells and causes growth inhibition and polarization of MCF7 cells","volume":"15","author":"Litzenburger","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.isci.2025.112354_bib36","doi-asserted-by":"crossref","first-page":"6890","DOI":"10.3748\/wjg.v25.i48.6890","article-title":"Comprehensive multi-omics analysis identified core molecular processes in esophageal cancer and revealed GNGT2 as a potential prognostic marker","volume":"25","author":"Liu","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.isci.2025.112354_bib37","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1177\/0748730412456367","article-title":"Cellular circadian clocks in mood disorders","volume":"27","author":"McCarthy","year":"2012","journal-title":"J. Biol. Rhythms"},{"key":"10.1016\/j.isci.2025.112354_bib38","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1101\/sqb.2007.72.031","article-title":"Role for the Clock gene in bipolar disorder","volume":"72","author":"McClung","year":"2007","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"10.1016\/j.isci.2025.112354_bib39","doi-asserted-by":"crossref","first-page":"9377","DOI":"10.1073\/pnas.0503584102","article-title":"Regulation of dopaminergic transmission and cocaine reward by the Clock gene","volume":"102","author":"McClung","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2025.112354_bib40","doi-asserted-by":"crossref","first-page":"6406","DOI":"10.1073\/pnas.0609625104","article-title":"Mania-like behavior induced by disruption of CLOCK","volume":"104","author":"Roybal","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2025.112354_bib41","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1093\/nsr\/nwz002","article-title":"BMAL1 knockout macaque monkeys display reduced sleep and psychiatric disorders","volume":"6","author":"Qiu","year":"2019","journal-title":"Natl. Sci. Rev."},{"key":"10.1016\/j.isci.2025.112354_bib42","doi-asserted-by":"crossref","first-page":"7257","DOI":"10.1038\/s41467-024-51716-9","article-title":"Prefrontal cortex molecular clock modulates development of depression-like phenotype and rapid antidepressant response in mice","volume":"15","author":"Sarrazin","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.isci.2025.112354_bib43","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1083\/jcb.200305131","article-title":"Impaired membrane resealing and autoimmune myositis in synaptotagmin VII-deficient mice","volume":"162","author":"Chakrabarti","year":"2003","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.isci.2025.112354_bib44","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/s11920-013-0387-y","article-title":"Immunity, inflammation, and bipolar disorder: diagnostic and therapeutic implications","volume":"15","author":"Hamdani","year":"2013","journal-title":"Curr. Psychiatry Rep."},{"key":"10.1016\/j.isci.2025.112354_bib45","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.neubiorev.2011.10.001","article-title":"Depression and type 2 diabetes: inflammatory mechanisms of a psychoneuroendocrine co-morbidity","volume":"36","author":"Stuart","year":"2012","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.isci.2025.112354_bib46","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.psyneuen.2017.05.018","article-title":"Diurnal cortisol slopes and mental and physical health outcomes: A systematic review and meta-analysis","volume":"83","author":"Adam","year":"2017","journal-title":"Psychoneuroendocrinology"},{"key":"10.1016\/j.isci.2025.112354_bib47","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nature15526","article-title":"Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder","volume":"527","author":"Mertens","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.isci.2025.112354_bib48","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1038\/mp.2016.260","article-title":"Neurons derived from patients with bipolar disorder divide into intrinsically different sub-populations of neurons, predicting the patients' responsiveness to lithium","volume":"23","author":"Stern","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"10.1016\/j.isci.2025.112354_bib49","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.cell.2014.09.040","article-title":"Generation of functional human pancreatic beta cells in vitro","volume":"159","author":"Pagliuca","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.isci.2025.112354_bib50","doi-asserted-by":"crossref","first-page":"11451","DOI":"10.1523\/JNEUROSCI.1758-09.2009","article-title":"Antidepressant actions of histone deacetylase inhibitors","volume":"29","author":"Covington","year":"2009","journal-title":"J. Neurosci."}],"container-title":["iScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004225006157?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004225006157?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T03:27:23Z","timestamp":1778902043000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589004225006157"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":50,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["S2589004225006157"],"URL":"https:\/\/doi.org\/10.1016\/j.isci.2025.112354","relation":{},"ISSN":["2589-0042"],"issn-type":[{"value":"2589-0042","type":"print"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Synaptotagmin-7 deficit causes insulin hypoactivity and contributes to behavioral alterations in mice","name":"articletitle","label":"Article Title"},{"value":"iScience","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.isci.2025.112354","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"112354"}}