{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:35:28Z","timestamp":1790742928086,"version":"4.1.0"},"reference-count":53,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010767","name":"Innovative Medicines Initiative 2 Joint Undertaking","doi-asserted-by":"publisher","award":["115881"],"award-info":[{"award-number":["115881"]}],"id":[{"id":"10.13039\/501100010767","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cystathionine beta synthase (CBS) catalyzes the first step of the transsulfuration pathway from homocysteine to cystathionine, and its deficiency leads to hyperhomocysteinemia (HHcy) in humans and rodents. To date, scarce information is available about the HHcy effect on insulin secretion, and the link between CBS activity and the setting of type 2 diabetes is still unknown. We aimed to decipher the consequences of an inborn defect in CBS on glucose homeostasis in mice. We used a mouse model heterozygous for CBS (CBS+\/\u2212) that presented a mild HHcy. Other groups were supplemented with methionine in drinking water to increase the mild to intermediate HHcy, and were submitted to a high-fat diet (HFD). We measured the food intake, body weight gain, body composition, glucose homeostasis, plasma homocysteine level, and CBS activity. We evidenced a defect in the stimulated insulin secretion in CBS+\/\u2212 mice with mild and intermediate HHcy, while mice with intermediate HHcy under HFD presented an improvement in insulin sensitivity that compensated for the decreased insulin secretion and permitted them to maintain a glucose tolerance similar to the CBS+\/+ mice. Islets isolated from CBS+\/\u2212 mice maintained their ability to respond to the elevated glucose levels, and we showed that a lower parasympathetic tone could, at least in part, be responsible for the insulin secretion defect. Our results emphasize the important role of Hcy metabolic enzymes in insulin secretion and overall glucose homeostasis.<\/jats:p>","DOI":"10.3390\/cells11111737","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:14:14Z","timestamp":1653437654000},"page":"1737","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Homocysteine Metabolism Pathway Is Involved in the Control of Glucose Homeostasis: A Cystathionine Beta Synthase Deficiency Study in Mouse"],"prefix":"10.3390","volume":"11","author":[{"given":"C\u00e9line","family":"Cruciani-Guglielmacci","sequence":"first","affiliation":[{"name":"Unit\u00e9 de Biologie Fonctionnelle et Adaptative, Universit\u00e9 Paris Cit\u00e9, CNRS, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Meneyrol","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Biologie Fonctionnelle et Adaptative, Universit\u00e9 Paris Cit\u00e9, CNRS, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Denom","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Biologie Fonctionnelle et Adaptative, Universit\u00e9 Paris Cit\u00e9, CNRS, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadim","family":"Kassis","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Biologie Fonctionnelle et Adaptative, Universit\u00e9 Paris Cit\u00e9, CNRS, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1089-2837","authenticated-orcid":false,"given":"Latif","family":"Rachdi","sequence":"additional","affiliation":[{"name":"Institut Cochin, Universit\u00e9 Paris Cit\u00e9, INSERM U1016, CNRS UMR 8104, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatna","family":"Makaci","sequence":"additional","affiliation":[{"name":"Institut Cochin, Universit\u00e9 Paris Cit\u00e9, INSERM U1016, CNRS UMR 8104, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Migrenne-Li","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Biologie Fonctionnelle et Adaptative, Universit\u00e9 Paris Cit\u00e9, CNRS, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Daubigney","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Biologie Fonctionnelle et Adaptative, Universit\u00e9 Paris Cit\u00e9, CNRS, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Georgiadou","sequence":"additional","affiliation":[{"name":"Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7677-7460","authenticated-orcid":false,"given":"Rapha\u00ebl G.","family":"Denis","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Biologie Fonctionnelle et Adaptative, Universit\u00e9 Paris Cit\u00e9, CNRS, 75013 Paris, France"},{"name":"Institut Cochin, Universit\u00e9 Paris Cit\u00e9, INSERM U1016, CNRS UMR 8104, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Rodriguez Sanchez-Archidona","sequence":"additional","affiliation":[{"name":"Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Louis","family":"Paul","sequence":"additional","affiliation":[{"name":"Georges Pompidou European Hospital Department of Biochemistry, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3738-0129","authenticated-orcid":false,"given":"Bernard","family":"Thorens","sequence":"additional","affiliation":[{"name":"Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy A.","family":"Rutter","sequence":"additional","affiliation":[{"name":"Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London W12 0NN, UK"},{"name":"Cardiometabolic Axis, CR-CHUM, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"},{"name":"Lee King Chian Medical School, Nanyang Technological University, Singapore 639798, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Magnan","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Biologie Fonctionnelle et Adaptative, Universit\u00e9 Paris Cit\u00e9, CNRS, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Le Stunff","sequence":"additional","affiliation":[{"name":"Institut des Neurosciences Paris-Saclay, CNRS UMR 9197, Universit\u00e9 Paris-Saclay, 91400 Saclay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Janel","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Biologie Fonctionnelle et Adaptative, Universit\u00e9 Paris Cit\u00e9, CNRS, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1023\/A:1005369109055","article-title":"Disorders of homocysteine metabolism","volume":"20","author":"Fowler","year":"1997","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/0955-2863(90)90070-2","article-title":"Methionine metabolism in mammals","volume":"1","author":"Finkelstein","year":"1990","journal-title":"J. Nutr. Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Nieraad, H., Pannwitz, N., de Bruin, N., Geisslinger, G., and Till, U. (2021). Hyperhomocysteinemia: Metabolic Role and Animal Studies with a Focus on Cognitive Performance and Decline\u2014A Review. Biomolecules, 11.","DOI":"10.3390\/biom11101546"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1002\/humu.24072","article-title":"Long-term uninterrupted enzyme replacement therapy prevents liver disease in murine model of severe homocystinuria","volume":"41","author":"Park","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1139\/cjpp-2014-0394","article-title":"The CBS\/CSE system: A potential therapeutic target in NAFLD?","volume":"93","author":"Sarna","year":"2015","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.diabres.2012.05.027","article-title":"Effect of folic acid supplementation on plasma total homocysteine levels and glycemic control in patients with type 2 diabetes: A systematic review and meta-analysis","volume":"98","author":"Sudchada","year":"2012","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9583","DOI":"10.1074\/jbc.M112.431627","article-title":"Hyperhomocysteinemia promotes insulin resistance by inducing endoplasmic reticulum stress in adipose tissue","volume":"288","author":"Li","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1073\/pnas.92.5.1585","article-title":"Mice deficient in cystathionine beta-synthase: Animal models for mild and severe homocyst(e)inemia","volume":"92","author":"Watanabe","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"807","DOI":"10.3389\/fneur.2019.00807","article-title":"Deciphering the Link between Hyperhomocysteinemia and Ceramide Metabolism in Alzheimer-Type Neurodegeneration","volume":"10","author":"Kassis","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.redox.2018.08.015","article-title":"Homocysteine-lowering gene therapy rescues signaling pathways in brain of mice with intermediate hyperhomocysteinemia","volume":"19","author":"Baloula","year":"2018","journal-title":"Redox Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.molmet.2017.01.009","article-title":"Molecular phenotyping of multiple mouse strains under metabolic challenge uncovers a role for Elovl2 in glucose-induced insulin secretion","volume":"6","author":"Bellini","year":"2017","journal-title":"Mol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4276","DOI":"10.1038\/emboj.2012.250","article-title":"Hypothalamic AgRP-neurons control peripheral substrate utilization and nutrient partitioning","volume":"31","author":"Denis","year":"2012","journal-title":"EMBO J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.molmet.2018.08.007","article-title":"Endocannabinoid and nitric oxide systems of the hypothalamic paraventricular nucleus mediate effects of NPY on energy expenditure","volume":"18","author":"Peterfi","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1042\/bj2980415","article-title":"Folate-deficiency-induced homocysteinaemia in rats: Disruption of S-adenosylmethionine\u2019s co-ordinate regulation of homocysteine metabolism","volume":"298","author":"Miller","year":"1994","journal-title":"Biochem. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S1570-0232(02)00497-X","article-title":"Methods for homocysteine analysis and biological relevance of the results","volume":"781","author":"Ducros","year":"2002","journal-title":"J. Chromatogr. B"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.4161\/cc.29250","article-title":"Dyrk1A induces pancreatic beta cell mass expansion and improves glucose tolerance","volume":"13","author":"Rachdi","year":"2014","journal-title":"Cell Cycle"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"102895","DOI":"10.1016\/j.ebiom.2020.102895","article-title":"A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob\/ob mice","volume":"58","author":"Amouyal","year":"2020","journal-title":"eBioMedicine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5165","DOI":"10.1038\/s41467-021-25423-8","article-title":"Intravital imaging of islet Ca2+ dynamics reveals enhanced beta cell connectivity after bariatric surgery in mice","volume":"12","author":"Akalestou","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"EdgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1111\/j.1365-2362.2007.01879.x","article-title":"Homocysteine threshold value based on cystathionine beta synthase and paraoxonase 1 activities in mice","volume":"37","author":"Hamelet","year":"2007","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1007\/s00125-020-05205-5","article-title":"Metabolic and functional specialisations of the pancreatic beta cell: Gene disallowance, mitochondrial metabolism and intercellular connectivity","volume":"63","author":"Rutter","year":"2020","journal-title":"Diabetologia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.2337\/diab.42.9.1273","article-title":"Signals derived from glucose metabolism are required for glucose regulation of pancreatic islet GLUT2 mRNA and protein","volume":"42","author":"Ferrer","year":"1993","journal-title":"Diabetes"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4182","DOI":"10.1172\/JCI68459","article-title":"Lipotoxicity disrupts incretin-regulated human beta cell connectivity","volume":"123","author":"Hodson","year":"2013","journal-title":"J. Clin. Invest."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.cmet.2016.06.020","article-title":"Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose","volume":"24","author":"Johnston","year":"2016","journal-title":"Cell. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"101355","DOI":"10.1016\/j.molmet.2021.101355","article-title":"Plasma triacylglycerols are biomarkers of beta-cell function in mice and humans","volume":"54","author":"Roujeau","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1097\/01.mpa.0000240613.43345.51","article-title":"Homocysteine-induced impairment of insulin secretion from clonal pancreatic BRIN-BD11 beta-cells is not prevented by catalase","volume":"34","author":"Patterson","year":"2007","journal-title":"Pancreas"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1530\/JOE-11-0461","article-title":"Enhancement of homocysteine toxicity to insulin-secreting BRIN-BD11 cells in combination with alloxan","volume":"214","author":"Scullion","year":"2012","journal-title":"J. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1089\/ars.2013.5309","article-title":"Production and Physiological Effects of Hydrogen Sulfide","volume":"20","author":"Kimura","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1093\/nar\/gkw745","article-title":"Reactive sulfur species regulate tRNA methylthiolation and contribute to insulin secretion","volume":"45","author":"Takahashi","year":"2017","journal-title":"Nucleic. Acids. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3281","DOI":"10.1016\/j.bbadis.2018.07.014","article-title":"Cystathionine beta synthase-hydrogen sulfide system in paraventricular nucleus reduced high fatty diet induced obesity and insulin resistance by brain-adipose axis","volume":"1864","author":"Zheng","year":"2018","journal-title":"Biochim. Biophys. Acta-Mol. Basis Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"448","DOI":"10.2741\/s37","article-title":"The central nervous system at the core of the regulation of energy homeostasis","volume":"1","author":"Luquet","year":"2009","journal-title":"Front. Biosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/dom.12346","article-title":"Neural regulation of pancreatic islet cell mass and function","volume":"16","author":"Thorens","year":"2014","journal-title":"Diabetes Obes. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.2337\/db15-0629","article-title":"The Brain\u2013to\u2013Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions","volume":"65","author":"Rosario","year":"2016","journal-title":"Diabetes"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.cmet.2006.04.009","article-title":"A critical role for beta cell M3 muscarinic acetylcholine receptors in regulating insulin release and blood glucose homeostasis in vivo","volume":"3","author":"Gautam","year":"2006","journal-title":"Cell Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1530\/eje.0.1490343","article-title":"Inhibition of insulin secretion via distinct signaling pathways in alpha2-adrenoceptor knockout mice","volume":"149","author":"Peterhoff","year":"2003","journal-title":"Eur. J. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.2337\/diabetes.52.11.2652","article-title":"Hypothesis: Shifting the equilibrium from activity to food leads to autonomic unbalance and the metabolic syndrome","volume":"52","author":"Kreier","year":"2003","journal-title":"Diabetes"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1161\/01.HYP.34.4.837","article-title":"Plasma homocysteine, aortic stiffness, and renal function in hypertensive patients","volume":"34","author":"Bortolotto","year":"1999","journal-title":"Hypertension."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.autneu.2013.10.006","article-title":"Moderate hyperhomocysteinemia provokes dysfunction of cardiovascular autonomic system and liver oxidative stress in rats","volume":"180","author":"Mendes","year":"2014","journal-title":"Auton. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.12659\/MSM.905002","article-title":"Hyperhomocysteinemia as a Metabolic Risk Factor for Glucose Intolerance Among High-Risk Groups of Chinese Adults","volume":"23","author":"Feng","year":"2017","journal-title":"Med. Sci. Monit."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0026-0495(96)90211-5","article-title":"Hyperhomocysteinemia following a methionine load in patients with non-insulin-dependent diabetes mellitus and macrovascular disease","volume":"45","author":"Munshi","year":"1996","journal-title":"Metabolism"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.2337\/diacare.20.12.1880","article-title":"Hyperhomocyst(e)inemia and Endothelial Dysfunction in IDDM","volume":"20","author":"Kohl","year":"1997","journal-title":"Diabetes Care"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1046\/j.1365-2796.2000.00592.x","article-title":"Plasma total homocysteine levels in subjects with hyperinsulinemia","volume":"247","author":"Kidron","year":"2000","journal-title":"J. Intern. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"E234","DOI":"10.1152\/ajpendo.00385.2018","article-title":"The autonomic nervous system regulates pancreatic beta-cell proliferation in adult male rats","volume":"317","author":"Moulle","year":"2019","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1210\/me.2011-1256","article-title":"Pax6 is crucial for beta-cell function, insulin biosynthesis, and glucose-induced insulin secretion","volume":"26","author":"Gosmain","year":"2012","journal-title":"Mol. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Hart, A.W., Mella, S., Mendrychowski, J., van Heyningen, V., and Kleinjan, D.A. (2013). The Developmental Regulator Pax6 Is Essential for Maintenance of Islet Cell Function in the Adult Mouse Pancreas. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054173"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1172\/JCI88015","article-title":"PAX6 maintains beta cell identity by repressing genes of alternative islet cell types","volume":"127","author":"Swisa","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.2337\/db16-1516","article-title":"Defining a Novel Role for the Pdx1 Transcription Factor in Islet beta-Cell Maturation and Proliferation During Weaning","volume":"66","author":"Spaeth","year":"2017","journal-title":"Diabetes"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1016\/j.celrep.2014.11.033","article-title":"Rfx6 maintains the functional identity of adult pancreatic beta cells","volume":"9","author":"Piccand","year":"2014","journal-title":"Cell Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3139","DOI":"10.1242\/dev.01875","article-title":"NKX6 transcription factor activity is required for alpha- and beta-cell development in the pancreas","volume":"132","author":"Henseleit","year":"2005","journal-title":"Development"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Noll, C., Planque, C., Ripoll, C., Guedj, F., Diez, A., Ducros, V., Belin, N., Duchon, A., Paul, J.-L., and Badel, A. (2009). DYRK1A, a Novel Determinant of the Methionine-Homocysteine Cycle in Different Mouse Models Overexpressing this Down-Syndrome-Associated Kinase. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007540"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12031-012-9835-0","article-title":"Mice deficient in cystathionine beta synthase display increased Dyrk1A and SAHH activities in brain","volume":"50","author":"Planque","year":"2013","journal-title":"J. Mol. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1007\/s00125-014-3174-3","article-title":"Dyrk1a haploinsufficiency induces diabetes in mice through decreased pancreatic beta cell mass","volume":"57","author":"Rachdi","year":"2014","journal-title":"Diabetologia"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/11\/1737\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:18:03Z","timestamp":1760138283000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/11\/1737"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,25]]},"references-count":53,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["cells11111737"],"URL":"https:\/\/doi.org\/10.3390\/cells11111737","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,25]]}}}