{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T02:51:18Z","timestamp":1785552678536,"version":"3.56.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"EXODIAB"},{"DOI":"10.13039\/501100012529","name":"Insamlingsstiftelsen Diabetes Wellness Network Sverige","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012529","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004973","name":"Barndiabetesfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004973","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006415","name":"Stiftelsen Familjen Ernfors Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006415","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008550","name":"Diabetesfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008550","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Aims\/hypothesis<\/jats:title>\n                <jats:p>ZBED6 (zinc finger, BED-type containing 6) is known to regulate muscle mass by suppression of <jats:italic>Igf2<\/jats:italic> gene transcription. In insulin-producing cell lines, ZBED6 maintains proliferative capacity at the expense of differentiation and beta cell function. The aim was to study the impact of <jats:italic>Zbed6<\/jats:italic> knockout on beta cell function and glucose tolerance in C57BL\/6 mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Beta cell area and proliferation were determined in <jats:italic>Zbed6<\/jats:italic> knockout mice using immunohistochemical analysis. Muscle and fat distribution were assessed using micro-computed tomography. Islet gene expression was assessed by RNA sequencing. Effects of a high-fat diet were analysed by glucose tolerance and insulin tolerance tests. ZBED6 was overexpressed in EndoC-\u03b2H1 cells and human islet cells using an adenoviral vector. Beta cell cell-cycle analysis, insulin release and mitochondrial function were studied in vitro using propidium iodide staining and flow cytometry, ELISA, the Seahorse technique, and the fluorescent probes JC-1 and MitoSox.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Islets from <jats:italic>Zbed6<\/jats:italic> knockout mice showed lowered expression of the cell cycle gene <jats:italic>Pttg1<\/jats:italic>, decreased beta cell proliferation and decreased beta cell area, which occurred independently from ZBED6 effects on <jats:italic>Igf2<\/jats:italic> gene expression. <jats:italic>Zbed6<\/jats:italic> knockout mice, but not wild-type mice, developed glucose intolerance when given a high-fat diet. The high-fat diet <jats:italic>Zbed6<\/jats:italic> knockout islets displayed upregulated expression of oxidative phosphorylation genes and genes associated with beta cell differentiation. In vitro<jats:italic>,<\/jats:italic> ZBED6 overexpression resulted in increased EndoC-\u03b2H1 cell proliferation and a reduced glucose-stimulated insulin release in human islets. ZBED6 also reduced mitochondrial JC-1 J-aggregate formation, mitochondrial oxygen consumption rates (OCR) and mitochondrial reactive oxygen species (ROS) production, both at basal and palmitate + high glucose-stimulated conditions. ZBED6-induced inhibition of OCR was not rescued by IGF2 addition. ZBED6 reduced levels of the mitochondrial regulator PPAR-\u03b3 related coactivator 1 protein (PRC) and bound its promoter\/enhancer region. Knockdown of PRC resulted in a lowered OCR.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions\/interpretation<\/jats:title>\n                <jats:p>It is concluded that ZBED6 is required for normal beta cell replication and also limits excessive beta cell mitochondrial activation in response to an increased functional demand. ZBED6 may act, at least in part, by restricting PRC-mediated mitochondrial activation\/ROS production, which may lead to protection against beta cell dysfunction and glucose intolerance in vivo.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s00125-021-05517-0","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T20:04:36Z","timestamp":1626984276000},"page":"2292-2305","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["ZBED6 counteracts high-fat diet-induced glucose intolerance by maintaining beta cell area and reducing excess mitochondrial activation"],"prefix":"10.1007","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6672-017X","authenticated-orcid":false,"given":"Xuan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4319-1738","authenticated-orcid":false,"given":"Shady","family":"Younis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Cen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Krizhanovskii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4085-6968","authenticated-orcid":false,"given":"Leif","family":"Andersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5926-5407","authenticated-orcid":false,"given":"Nils","family":"Welsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,22]]},"reference":[{"key":"5517_CR1","doi-asserted-by":"publisher","first-page":"e1000256","DOI":"10.1371\/journal.pbio.1000256","volume":"7","author":"E Markljung","year":"2009","unstructured":"Markljung E, Jiang L, Jaffe JD et al (2009) ZBED6, a novel transcription factor derived from a domesticated DNA transposon regulates IGF2 expression and muscle growth. PLoS Biol 7:e1000256. https:\/\/doi.org\/10.1371\/journal.pbio.1000256","journal-title":"PLoS Biol"},{"key":"5517_CR2","doi-asserted-by":"publisher","first-page":"10250","DOI":"10.1096\/fj.201901321R","volume":"34","author":"S Younis","year":"2020","unstructured":"Younis S, Naboulsi R, Wang X et al (2020) The importance of the ZBED6-IGF2 axis for metabolic regulation in mouse myoblast cells. FASEB J 34:10250\u201310266. https:\/\/doi.org\/10.1096\/fj.201901321R","journal-title":"FASEB J"},{"key":"5517_CR3","doi-asserted-by":"publisher","first-page":"E2048","DOI":"10.1073\/pnas.1719278115","volume":"115","author":"S Younis","year":"2018","unstructured":"Younis S, Schonke M, Massart J et al (2018) The ZBED6-IGF2 axis has a major effect on growth of skeletal muscle and internal organs in placental mammals. Proc Natl Acad Sci U S A 115:E2048\u2013E2057. https:\/\/doi.org\/10.1073\/pnas.1719278115","journal-title":"Proc Natl Acad Sci U S A"},{"key":"5517_CR4","doi-asserted-by":"publisher","first-page":"15997","DOI":"10.1073\/pnas.1303625110","volume":"110","author":"X Wang","year":"2013","unstructured":"Wang X, Jiang L, Wallerman O et al (2013) Transcription factor ZBED6 affects gene expression, proliferation, and cell death in pancreatic beta cells. Proc Natl Acad Sci U S A 110:15997\u201316002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"5517_CR5","doi-asserted-by":"publisher","first-page":"19006","DOI":"10.1038\/srep19006","volume":"6","author":"X Wang","year":"2016","unstructured":"Wang X, Xie B, Qi Y et al (2016) Knock-down of ZBED6 in insulin-producing cells promotes N-cadherin junctions between beta-cells and neural crest stem cells in vitro. Sci Rep 6:19006","journal-title":"Sci Rep"},{"key":"5517_CR6","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1096\/fj.201600835R","volume":"33","author":"X Wang","year":"2019","unstructured":"Wang X, Jiang L, Wallerman O et al (2019) ZBED6 negatively regulates insulin production, neuronal differentiation, and cell aggregation in MIN6 cells. FASEB J 33:88\u2013100","journal-title":"FASEB J"},{"key":"5517_CR7","doi-asserted-by":"publisher","first-page":"532","DOI":"10.3389\/fendo.2018.00532","volume":"9","author":"K Erion","year":"2018","unstructured":"Erion K, Corkey BE (2018) Beta-cell failure or beta-cell abuse? Front Endocrinol (Lausanne) 9:532","journal-title":"Front Endocrinol (Lausanne)"},{"key":"5517_CR8","doi-asserted-by":"publisher","unstructured":"Trico D, Natali A, Arslanian S, Mari A, Ferrannini E (2018) Identification, pathophysiology, and clinical implications of primary insulin hypersecretion in nondiabetic adults and adolescents. JCI Insight 3. https:\/\/doi.org\/10.1172\/jci.insight.124912","DOI":"10.1172\/jci.insight.124912"},{"key":"5517_CR9","doi-asserted-by":"publisher","first-page":"28461","DOI":"10.1038\/srep28461","volume":"6","author":"S Tiwari","year":"2016","unstructured":"Tiwari S, Roel C, Tanwir M et al (2016) Definition of a Skp2-c-Myc pathway to expand human beta-cells. Sci Rep 6:28461","journal-title":"Sci Rep"},{"key":"5517_CR10","doi-asserted-by":"publisher","first-page":"35","DOI":"10.3389\/fgene.2017.00035","volume":"8","author":"CS Hunter","year":"2017","unstructured":"Hunter CS, Stein RW (2017) Evidence for loss in identity, de-differentiation, and trans-differentiation of islet beta-cells in type 2 diabetes. Front Genet 8:35. https:\/\/doi.org\/10.3389\/fgene.2017.00035","journal-title":"Front Genet"},{"key":"5517_CR11","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1038\/414792a","volume":"414","author":"D Mathis","year":"2001","unstructured":"Mathis D, Vence L, Benoist C (2001) Beta-cell death during progression to diabetes. Nature 414:792\u2013798. https:\/\/doi.org\/10.1038\/414792a","journal-title":"Nature"},{"key":"5517_CR12","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.2337\/dc14-0396","volume":"37","author":"PA Halban","year":"2014","unstructured":"Halban PA, Polonsky KS, Bowden DW et al (2014) Beta-cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment. Diabetes Care 37:1751\u20131758. https:\/\/doi.org\/10.2337\/dc14-0396","journal-title":"Diabetes Care"},{"key":"5517_CR13","doi-asserted-by":"publisher","first-page":"E3808","DOI":"10.1073\/pnas.1722333115","volume":"115","author":"S Younis","year":"2018","unstructured":"Younis S, Kamel W, Falkeborn T et al (2018) Multiple nuclear-replicating viruses require the stress-induced protein ZC3H11A for efficient growth. Proc Natl Acad Sci U S A 115:E3808\u2013E3816. https:\/\/doi.org\/10.1073\/pnas.1722333115","journal-title":"Proc Natl Acad Sci U S A"},{"key":"5517_CR14","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1007\/BF01228134","volume":"14","author":"A Andersson","year":"1978","unstructured":"Andersson A (1978) Isolated mouse pancreatic islets in culture: effects of serum and different culture media on the insulin production of the islets. Diabetologia 14:397\u2013404. https:\/\/doi.org\/10.1007\/BF01228134","journal-title":"Diabetologia"},{"key":"5517_CR15","doi-asserted-by":"publisher","first-page":"R25","DOI":"10.1186\/gb-2010-11-3-r25","volume":"11","author":"MD Robinson","year":"2010","unstructured":"Robinson MD, Oshlack A (2010) A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol 11:R25. https:\/\/doi.org\/10.1186\/gb-2010-11-3-r25","journal-title":"Genome Biol"},{"key":"5517_CR16","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu G, Wang L, Han Y, He QY (2012) clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16:284\u2013287. https:\/\/doi.org\/10.1089\/omi.2011.0118","journal-title":"OMICS"},{"key":"5517_CR17","doi-asserted-by":"publisher","first-page":"3589","DOI":"10.1172\/JCI58447","volume":"121","author":"P Ravassard","year":"2011","unstructured":"Ravassard P, Hazhouz Y, Pechberty S et al (2011) A genetically engineered human pancreatic beta cell line exhibiting glucose-inducible insulin secretion. J Clin Invest 121:3589\u20133597. https:\/\/doi.org\/10.1172\/JCI58447","journal-title":"J Clin Invest"},{"key":"5517_CR18","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S0303-7207(02)00009-6","volume":"190","author":"A Barbu","year":"2002","unstructured":"Barbu A, Welsh N, Saldeen J (2002) Cytokine-induced apoptosis and necrosis are preceded by disruption of the mitochondrial membrane potential (Deltapsi(m)) in pancreatic RINm5F cells: prevention by Bcl-2. Mol Cell Endocrinol 190:75\u201382. https:\/\/doi.org\/10.1016\/S0303-7207(02)00009-6","journal-title":"Mol Cell Endocrinol"},{"key":"5517_CR19","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s12986-016-0119-5","volume":"13","author":"J Cen","year":"2016","unstructured":"Cen J, Sargsyan E, Bergsten P (2016) Fatty acids stimulate insulin secretion from human pancreatic islets at fasting glucose concentrations via mitochondria-dependent and -independent mechanisms. Nutr Metab 13:59","journal-title":"Nutr Metab"},{"key":"5517_CR20","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1007\/s00335-007-9054-0","volume":"18","author":"ED Hughes","year":"2007","unstructured":"Hughes ED, Qu YY, Genik SJ et al (2007) Genetic variation in C57BL\/6 ES cell lines and genetic instability in the Bruce4 C57BL\/6 ES cell line. Mamm Genome 18:549\u2013558. https:\/\/doi.org\/10.1007\/s00335-007-9054-0","journal-title":"Mamm Genome"},{"key":"5517_CR21","doi-asserted-by":"publisher","first-page":"e0159165","DOI":"10.1371\/journal.pone.0159165","volume":"11","author":"C Attan\u00e9","year":"2016","unstructured":"Attan\u00e9 C, Peyot M-L, Lussier R et al (2016) Differential insulin secretion of high-fat diet-fed C57BL\/6NN and C57BL\/6NJ mice: implications of mixed genetic background in metabolic studies. PLoS One 11:e0159165. https:\/\/doi.org\/10.1371\/journal.pone.0159165","journal-title":"PLoS One"},{"key":"5517_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mce.2008.07.006","volume":"294","author":"AS Bernardo","year":"2008","unstructured":"Bernardo AS, Hay CW, Docherty K (2008) Pancreatic transcription factors and their role in the birth, life and survival of the pancreatic beta cell. Mol Cell Endocrinol 294:1\u20139. https:\/\/doi.org\/10.1016\/j.mce.2008.07.006","journal-title":"Mol Cell Endocrinol"},{"key":"5517_CR23","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.redox.2017.07.012","volume":"13","author":"N Li","year":"2017","unstructured":"Li N, Karaca M, Maechler P (2017) Upregulation of UCP2 in beta-cells confers partial protection against both oxidative stress and glucotoxicity. Redox Biol 13:541\u2013549. https:\/\/doi.org\/10.1016\/j.redox.2017.07.012","journal-title":"Redox Biol"},{"key":"5517_CR24","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.bbrc.2006.06.140","volume":"347","author":"YM Chung","year":"2006","unstructured":"Chung YM, Kim JS, Yoo YD (2006) A novel protein, Romo1, induces ROS production in the mitochondria. Biochem Biophys Res Commun 347:649\u2013655. https:\/\/doi.org\/10.1016\/j.bbrc.2006.06.140","journal-title":"Biochem Biophys Res Commun"},{"key":"5517_CR25","doi-asserted-by":"publisher","first-page":"e94187","DOI":"10.1371\/journal.pone.0094187","volume":"9","author":"L Jiang","year":"2014","unstructured":"Jiang L, Wallerman O, Younis S et al (2014) ZBED6 modulates the transcription of myogenic genes in mouse myoblast cells. PLoS One 9:e94187. https:\/\/doi.org\/10.1371\/journal.pone.0094187","journal-title":"PLoS One"},{"key":"5517_CR26","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1111\/febs.13175","volume":"282","author":"JA Villena","year":"2015","unstructured":"Villena JA (2015) New insights into PGC-1 coactivators: redefining their role in the regulation of mitochondrial function and beyond. FEBS J 282:647\u2013672. https:\/\/doi.org\/10.1111\/febs.13175","journal-title":"FEBS J"},{"key":"5517_CR27","doi-asserted-by":"publisher","first-page":"5596","DOI":"10.1038\/sj.onc.1210339","volume":"26","author":"Y Tong","year":"2007","unstructured":"Tong Y, Tan Y, Zhou C, Melmed S (2007) Pituitary tumor transforming gene interacts with Sp1 to modulate G1\/S cell phase transition. Oncogene 26:5596\u20135605. https:\/\/doi.org\/10.1038\/sj.onc.1210339","journal-title":"Oncogene"},{"key":"5517_CR28","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1677\/ERC-08-0012","volume":"15","author":"F Salehi","year":"2008","unstructured":"Salehi F, Kovacs K, Scheithauer BW, Lloyd RV, Cusimano M (2008) Pituitary tumor-transforming gene in endocrine and other neoplasms: a review and update. Endocr Relat Cancer 15:721\u2013743. https:\/\/doi.org\/10.1677\/ERC-08-0012","journal-title":"Endocr Relat Cancer"},{"key":"5517_CR29","doi-asserted-by":"publisher","first-page":"3428","DOI":"10.1073\/pnas.0638052100","volume":"100","author":"Z Wang","year":"2003","unstructured":"Wang Z, Moro E, Kovacs K, Yu R, Melmed S (2003) Pituitary tumor transforming gene-null male mice exhibit impaired pancreatic beta cell proliferation and diabetes. Proc Natl Acad Sci U S A 100:3428\u20133432","journal-title":"Proc Natl Acad Sci U S A"},{"key":"5517_CR30","doi-asserted-by":"publisher","first-page":"e0247888","DOI":"10.1371\/journal.pone.0247888","volume":"3","author":"P Seiron","year":"2021","unstructured":"Seiron P, Stenwall A, Hedin A et al (2021) Transcriptional analysis of islets of Langerhans from organ donors of different ages. PLoSOne 3:e0247888","journal-title":"PLoSOne"},{"key":"5517_CR31","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.mce.2015.07.015","volume":"414","author":"RG Fred","year":"2015","unstructured":"Fred RG, Kappe C, Ameur A et al (2015) Role of the AMP kinase in cytokine-induced human EndoC-betaH1 cell death. Mol Cell Endocrinol 414:53\u201363. https:\/\/doi.org\/10.1016\/j.mce.2015.07.015","journal-title":"Mol Cell Endocrinol"},{"key":"5517_CR32","doi-asserted-by":"publisher","first-page":"77","DOI":"10.3109\/03009734.2015.1109012","volume":"121","author":"M Welsh","year":"2016","unstructured":"Welsh M (2016) Claes Hellerstr\u00f6m and Cartesian diver microrespirometry. Ups J Med Sci 121:77\u201380. https:\/\/doi.org\/10.3109\/03009734.2015.1109012","journal-title":"Ups J Med Sci"},{"key":"5517_CR33","doi-asserted-by":"publisher","first-page":"16804","DOI":"10.1074\/jbc.R117.789271","volume":"292","author":"HS Wong","year":"2017","unstructured":"Wong HS, Dighe PA, Mezera V, Monternier PA, Brand MD (2017) Production of superoxide and hydrogen peroxide from specific mitochondrial sites under different bioenergetic conditions. J Biol Chem 292:16804\u201316809. https:\/\/doi.org\/10.1074\/jbc.R117.789271","journal-title":"J Biol Chem"},{"key":"5517_CR34","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1021\/pr100892r","volume":"10","author":"HJ Kim","year":"2011","unstructured":"Kim HJ, Kim JH, Noh S et al (2011) Metabolomic analysis of livers and serum from high-fat diet induced obese mice. J Proteome Res 10:722\u2013731. https:\/\/doi.org\/10.1021\/pr100892r","journal-title":"J Proteome Res"},{"key":"5517_CR35","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.redox.2015.08.016","volume":"6","author":"A Gorlach","year":"2015","unstructured":"Gorlach A, Dimova EY, Petry A et al (2015) Reactive oxygen species, nutrition, hypoxia and diseases: problems solved? Redox Biol 6:372\u2013385. https:\/\/doi.org\/10.1016\/j.redox.2015.08.016","journal-title":"Redox Biol"},{"key":"5517_CR36","doi-asserted-by":"publisher","first-page":"3422","DOI":"10.1210\/endo.140.8.6908","volume":"140","author":"C Carlsson","year":"1999","unstructured":"Carlsson C, Borg LA, Welsh N (1999) Sodium palmitate induces partial mitochondrial uncoupling and reactive oxygen species in rat pancreatic islets in vitro. Endocrinology 140:3422\u20133428. https:\/\/doi.org\/10.1210\/endo.140.8.6908","journal-title":"Endocrinology"},{"key":"5517_CR37","doi-asserted-by":"publisher","first-page":"4666","DOI":"10.1210\/en.2012-1296","volume":"153","author":"H Weiss","year":"2012","unstructured":"Weiss H, Wester-Rosenloef L, Koch C et al (2012) The mitochondrial Atp8 mutation induces mitochondrial ROS generation, secretory dysfunction, and beta-cell mass adaptation in conplastic B6-mtFVB mice. Endocrinology 153:4666\u20134676. https:\/\/doi.org\/10.1210\/en.2012-1296","journal-title":"Endocrinology"},{"key":"5517_CR38","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.2337\/db18-0856","volume":"68","author":"T Mezza","year":"2019","unstructured":"Mezza T, Cinti F, Cefalo CMA, Pontecorvi A, Kulkarni RN, Giaccari A (2019) Beta-cell fate in human insulin resistance and type 2 diabetes: a perspective on islet plasticity. Diabetes 68:1121\u20131129. https:\/\/doi.org\/10.2337\/db18-0856","journal-title":"Diabetes"}],"container-title":["Diabetologia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-021-05517-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00125-021-05517-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-021-05517-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T07:04:27Z","timestamp":1630998267000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00125-021-05517-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,22]]},"references-count":38,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["5517"],"URL":"https:\/\/doi.org\/10.1007\/s00125-021-05517-0","relation":{},"ISSN":["0012-186X","1432-0428"],"issn-type":[{"value":"0012-186X","type":"print"},{"value":"1432-0428","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,22]]},"assertion":[{"value":"10 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}