{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,4]],"date-time":"2024-08-04T05:53:44Z","timestamp":1722750824821},"reference-count":45,"publisher":"Georg Thieme Verlag KG","issue":"09","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\nBackground High-fat-diet induces pancreatic \u03b2-cell compensatory proliferation, and impairments in pancreatic \u03b2-cell proliferation and function can lead to defects in insulin secretion and diabetes. NFATc3 is important for HFD-induced adipose tissue inflammation. But it is unknown whether NFATc3 is required for \u03b2 cell compensatory growth in mice fed with HFD.<\/jats:p><jats:p>\nMethods NFATc3 mRNA and protein expression levels were quantified by RT-qPCR and Western blotting, respectively, in pancreatic islets of WT mice fed on HFD for 12\u201320 weeks. Adenoviral-mediated overexpression of NFATc3 were conducted in Min6 cells and cultured primary mouse islets. NFATc3-\/- mice and WT control mice were fed with HFD and metabolic and functional parameters were measured.<\/jats:p><jats:p>\nResults We observed that the NFATc3 expression level was reduced in the islets of high-fat-diet (HFD)-fed mice. Adenovirus-mediated overexpression of NFATc3 enhanced glucose-stimulated insulin secretion and \u03b2-cell gene expression in cultured primary mouse islets. Nfatc3-\/- mice initially developed similar glucose tolerance at 2\u20134 weeks after HFD feeding than HFD-fed WT mice, but Nfatc3-\/- mice developed improved glucose tolerance and insulin sensitivity after 8 weeks of HFD feeding compared to Nfatc3+\/+fed with HFD. Furthermore, Nfatc3-\/- mice on HFD exhibited decreased \u03b2-cell mass and reduced expression of genes important for \u03b2-cell proliferation and function compared to Nfatc3+\/+mice on HFD.<\/jats:p><jats:p>\nConclusions The findings suggested that NFATc3 plays a role in maintaining the pancreatic \u03b2-cell compensatory growth and gene expression in response to obesity.<\/jats:p>","DOI":"10.1055\/a-1008-9110","type":"journal-article","created":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T23:16:30Z","timestamp":1569280590000},"page":"651-660","source":"Crossref","is-referenced-by-count":3,"title":["Reduced Compensatory \u03b2-Cell Proliferation in Nfatc3-Deficient Mice Fed on High-Fat Diet"],"prefix":"10.1055","volume":"129","author":[{"given":"Li","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengli","family":"He","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hairong","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luo","family":"Hai","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yabin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiguang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Shan","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"Bristol-Myers Squibb Company, Princeton, NJ 08540, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2019,9,23]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.2337\/diabetes.53.suppl_3.S16","article-title":"Five stages of evolving beta-cell dysfunction during progression to diabetes","volume":"53","author":"G C Weir","year":"2004","journal-title":"Diabetes"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"S154","DOI":"10.2337\/diabetes.50.2007.S154","article-title":"Beta-cell adaptation and decompensation during the progression of diabetes","volume":"50","author":"G C Weir","year":"2001","journal-title":"Diabetes"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2174\/157339913804143225","article-title":"Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes","volume":"9","author":"Z Fu","year":"2013","journal-title":"Curr Diabetes Rev"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"6281","DOI":"10.3390\/ijms16036281","article-title":"Role of pancreatic transcription factors in maintenance of mature beta-cell function","volume":"16","author":"H Kaneto","year":"2015","journal-title":"Int J Mol Sci"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1186\/s13287-017-0694-z","article-title":"PDX1, Neurogenin-3, and MAFA: Critical transcription regulators for beta cell development and regeneration","volume":"8","author":"Y Zhu","year":"2017","journal-title":"Stem Cell Res Ther"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1677\/JME-06-0053","article-title":"Molecular regulation of pancreatic beta-cell mass development, maintenance, and expansion","volume":"38","author":"A M Ackermann","year":"2007","journal-title":"J Mol Endocrinol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.cell.2012.07.029","article-title":"Pancreatic beta cell dedifferentiation as a mechanism of diabetic beta cell failure","volume":"150","author":"C Talchai","year":"2012","journal-title":"Cell"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1073\/pnas.97.4.1607","article-title":"neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas","volume":"97","author":"G Gradwohl","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"e1003274","DOI":"10.1371\/journal.pgen.1003274","article-title":"Nkx6.1 controls a gene regulatory network required for establishing and maintaining pancreatic Beta cell identity","volume":"9","author":"A E Schaffer","year":"2013","journal-title":"PLoS Genet"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"987","DOI":"10.2337\/db09-0838","article-title":"Cyclin D2 is essential for the compensatory beta-cell hyperplastic response to insulin resistance in rodents","volume":"59","author":"S Georgia","year":"2010","journal-title":"Diabetes"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1080\/15384101.2017.1319999","article-title":"Cyclin D2 is sufficient to drive beta cell self-renewal and regeneration","volume":"16","author":"S I Tschen","year":"2017","journal-title":"Cell Cycle"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"3752","DOI":"10.1128\/MCB.25.9.3752-3762.2005","article-title":"Cyclins D2 and D1 are essential for postnatal pancreatic beta-cell growth","volume":"25","author":"J A Kushner","year":"2005","journal-title":"Mol Cell Biol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"981","DOI":"10.2337\/db15-0529","article-title":"Glucose induces mouse beta-cell proliferation via IRS2, MTOR, and Cyclin D2 but not the insulin receptor","volume":"65","author":"R E Stamateris","year":"2016","journal-title":"Diabetes"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1146\/annurev.immunol.15.1.707","article-title":"Transcription factors of the NFAT family: regulation and function","volume":"15","author":"A Rao","year":"1997","journal-title":"Annu Rev Immunol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S1074-7613(00)80612-3","article-title":"The transcription factor NFAT4 is involved in the generation and survival of T cells","volume":"9","author":"M Oukka","year":"1998","journal-title":"Immunity"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1161\/01.RES.0000109415.17511.18","article-title":"Calcineurin\/NFAT coupling participates in pathological, but not physiological, cardiac hypertrophy","volume":"94","author":"B J Wilkins","year":"2004","journal-title":"Circ Res"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"9936","DOI":"10.1128\/MCB.25.22.9936-9948.2005","article-title":"The DnaJ-related factor Mrj interacts with nuclear factor of activated T cells c3 and mediates transcriptional repression through class II histone deacetylase recruitment","volume":"25","author":"Y S Dai","year":"2005","journal-title":"Mol Cell Biol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"H2382","DOI":"10.1152\/ajpheart.00132.2008","article-title":"NFATc3 is required for intermittent hypoxia-induced hypertension","volume":"294","author":"S de Frutos","year":"2008","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"H356","DOI":"10.1152\/ajpheart.00341.2010","article-title":"NFATc3 contributes to intermittent hypoxia-induced arterial remodeling in mice","volume":"299","author":"S de Frutos","year":"2010","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1159\/000362647","article-title":"The transcription factor nuclear factor of activated T cells c3 modulates the function of macrophages in sepsis","volume":"6","author":"R Ranjan","year":"2014","journal-title":"J Innate Immun"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"e1006466","DOI":"10.1371\/journal.pgen.1006466","article-title":"The Transcription factor nfatc2 regulates beta-cell proliferation and genes associated with type 2 diabetes in mouse and human islets","volume":"12","author":"M P Keller","year":"2016","journal-title":"PLoS Genet"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"3835","DOI":"10.1172\/JCI91761","article-title":"Age-dependent human beta cell proliferation induced by glucagon-like peptide 1 and calcineurin signaling","volume":"127","author":"C Dai","year":"2017","journal-title":"J Clin Invest"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1530\/JME-18-0070","article-title":"NFATc3 Deficiency reduces the classical activation of adipose tissue macrophages","volume":"61","author":"L Hu","year":"2018","journal-title":"J Mol Endocrinol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1161\/01.RES.86.3.255","article-title":"Calcineurin-mediated hypertrophy protects cardiomyocytes from apoptosis in vitro and in vivo: An apoptosis-independent model of dilated heart failure","volume":"86","author":"L J De Windt","year":"2000","journal-title":"Circ Res"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"e99049","DOI":"10.1371\/journal.pone.0099049","article-title":"Transcription factor Ets1 regulates expression of thioredoxin-interacting protein and inhibits insulin secretion in pancreatic beta-cells","volume":"9","author":"Y Luo","year":"2014","journal-title":"PLoS One"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.2337\/db12-0249","article-title":"Disruption of growth factor receptor-binding protein 10 in the pancreas enhances beta-cell proliferation and protects mice from streptozotocin-induced beta-cell apoptosis","volume":"61","author":"J Zhang","year":"2012","journal-title":"Diabetes"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nature05097","article-title":"Calcineurin\/NFAT signalling regulates pancreatic beta-cell growth and function","volume":"443","author":"J J Heit","year":"2006","journal-title":"Nature"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"e50128","DOI":"10.1371\/journal.pone.0050128","article-title":"PPAR-gamma activation increases insulin secretion through the up-regulation of the free fatty acid receptor GPR40 in pancreatic beta-cells","volume":"8","author":"H S Kim","year":"2013","journal-title":"PLoS One"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.cell.2012.02.010","article-title":"Diabetes mellitus and the beta cell: The last ten years","volume":"148","author":"F M Ashcroft","year":"2012","journal-title":"Cell"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2003.09.026","article-title":"Palmitate-induced Ca2+-signaling in pancreatic beta-cells","volume":"212","author":"O Remizov","year":"2003","journal-title":"Mol Cell Endocrinol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.ceca.2011.08.005","article-title":"The central role of calcium in the effects of cytokines on beta-cell function: implications for type 1 and type 2 diabetes","volume":"50","author":"J W Ramadan","year":"2011","journal-title":"Cell Calcium"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.2337\/db11-0341","article-title":"Specific glucose-induced control of insulin receptor substrate-2 expression is mediated via Ca2+-dependent calcineurin\/NFAT signaling in primary pancreatic islet beta-cells","volume":"60","author":"D Demozay","year":"2011","journal-title":"Diabetes"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.devcel.2012.05.014","article-title":"Neonatal beta cell development in mice and humans is regulated by calcineurin\/NFAT","volume":"23","author":"W R Goodyer","year":"2012","journal-title":"Dev Cell"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"691","DOI":"10.2337\/diabetes.51.3.691","article-title":"NFAT regulates insulin gene promoter activity in response to synergistic pathways induced by glucose and glucagon-like peptide-1","volume":"51","author":"M C Lawrence","year":"2002","journal-title":"Diabetes"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/nri1632","article-title":"NFAT proteins: key regulators of T-cell development and function","volume":"5","author":"F Macian","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1210\/er.2006-0004","article-title":"Molecular control of cell cycle progression in the pancreatic beta-cell","volume":"27","author":"I Cozar-Castellano","year":"2006","journal-title":"Endocr Rev"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1146\/annurev.cellbio.22.010305.104425","article-title":"Intrinsic regulators of pancreatic beta-cell proliferation","volume":"22","author":"J J Heit","year":"2006","journal-title":"Annu Rev Cell Dev Biol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2008.07.006","article-title":"Pancreatic transcription factors and their role in the birth, life and survival of the pancreatic beta cell","volume":"294","author":"A S Bernardo","year":"2008","journal-title":"Mol Cell Endocrinol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.jss.2008.07.023","article-title":"NFAT4 deficiency results in incomplete liver regeneration following partial hepatectomy","volume":"154","author":"K B Pierre","year":"2009","journal-title":"J Surg Res"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.jpurol.2014.04.002","article-title":"Genetic or pharmacologic disruption of the calcineurin-nuclear factor of activated T-cells axis prevents social stress-induced voiding dysfunction in a murine model","volume":"10","author":"C J Long","year":"2014","journal-title":"J Pediatr Urol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"5735","DOI":"10.1128\/MCB.00249-06","article-title":"FoxA2, Nkx2.2, and PDX-1 regulate islet beta-cell-specific mafA expression through conserved sequences located between base pairs -8118 and -7750 upstream from the transcription start site","volume":"26","author":"J C Raum","year":"2006","journal-title":"Mol Cell Biol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1507\/endocrj.KR-101","article-title":"Roles and regulation of transcription factor MafA in islet beta-cells","volume":"54","author":"S Aramata","year":"2007","journal-title":"Endocr J"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1507\/endocrj.KR-109","article-title":"Role of FoxO proteins in pancreatic beta cells","volume":"54","author":"T Kitamura","year":"2007","journal-title":"Endocr J"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1677\/JME-08-0062","article-title":"Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression","volume":"41","author":"C C Martin","year":"2008","journal-title":"J Mol Endocrinol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"26751","DOI":"10.1074\/jbc.M503158200","article-title":"ERK1\/2-dependent activation of transcription factors required for acute and chronic effects of glucose on the insulin gene promoter","volume":"280","author":"M C Lawrence","year":"2005","journal-title":"J Biol Chem"}],"container-title":["Experimental and Clinical Endocrinology &amp; Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1008-9110.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T22:49:53Z","timestamp":1630709393000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1008-9110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,23]]},"references-count":45,"journal-issue":{"issue":"09","published-online":{"date-parts":[[2021,9,3]]},"published-print":{"date-parts":[[2021,9]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1008-9110","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0947-7349","1439-3646"],"issn-type":[{"value":"0947-7349","type":"print"},{"value":"1439-3646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,23]]}}}