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Key transcriptional regulators link genetic susceptibility to mitochondrial dysfunction in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). These disruptions impair mitophagy, mitochondrial translation and redox homeostasis. Therapeutic strategies that restore mitochondrial function, including mitophagy enhancers, mitochondrial antioxidants, and transcriptional regulators, have shown potential in preserving \u03b2-cell integrity. As mitochondrial failure precedes \u03b2-cell loss, targeting mitochondrial pathways may represent a critical approach to modifying diabetes progression.<\/jats:p>","DOI":"10.3390\/cells14231861","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T10:04:57Z","timestamp":1764151497000},"page":"1861","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["\u03b2-Cell Mitochondrial Dysfunction: Underlying Mechanisms and Potential Therapeutic Strategies"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3419-4118","authenticated-orcid":false,"given":"Radwan","family":"Darwish","sequence":"first","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland-Medical University of Bahrain, Busaiteen P.O. 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Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/emboj.2008.302","article-title":"Matrix alkalinization: A novel mitochondrial signal for sustained pancreatic beta-cell activation","volume":"28","author":"Wiederkehr","year":"2009","journal-title":"EMBO J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"E1298","DOI":"10.1152\/ajpendo.90493.2008","article-title":"Channel regulation of glucose sensing in the pancreatic beta-cell","volume":"295","author":"Hiriart","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ceca.2007.11.004","article-title":"Impact of mitochondrial calcium on the coupling of metabolism to insulin secretion in the pancreatic beta-cell","volume":"44","author":"Wiederkehr","year":"2008","journal-title":"Cell Calcium"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6017","DOI":"10.1007\/s00018-021-03871-1","article-title":"Distinct states of proinsulin misfolding in MIDY","volume":"78","author":"Haataja","year":"2021","journal-title":"Cell Mol. Life Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.freeradbiomed.2014.07.037","article-title":"Oxidative protein folding: From thiol-disulfide exchange reactions to the redox poise of the endoplasmic reticulum","volume":"80","author":"Hudson","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e178725","DOI":"10.1172\/jci.insight.178725","article-title":"A metabolic redox relay supports ER proinsulin export in pancreatic islet beta cells","volume":"9","author":"Rohli","year":"2024","journal-title":"JCI Insight"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/s41580-020-00317-7","article-title":"Mechanisms controlling pancreatic islet cell function in insulin secretion","volume":"22","author":"Campbell","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1080\/15384101.2017.1361069","article-title":"Cell cycle-related metabolism and mitochondrial dynamics in a replication-competent pancreatic beta-cell line","volume":"16","author":"Montemurro","year":"2017","journal-title":"Cell Cycle"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.cmet.2020.10.007","article-title":"Pyruvate Kinase Controls Signal Strength in the Insulin Secretory Pathway","volume":"32","author":"Lewandowski","year":"2020","journal-title":"Cell Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e79422","DOI":"10.7554\/eLife.79422","article-title":"beta-cell deletion of the PKm1 and PKm2 isoforms of pyruvate kinase in mice reveals their essential role as nutrient sensors for the K(ATP) channel","volume":"11","author":"Foster","year":"2022","journal-title":"eLife"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"112394","DOI":"10.1016\/j.celrep.2023.112394","article-title":"A plasma membrane-associated glycolytic metabolon is functionally coupled to K(ATP) channels in pancreatic alpha and beta cells from humans and mice","volume":"42","author":"Ho","year":"2023","journal-title":"Cell Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.mce.2011.07.016","article-title":"Mitochondrial signals drive insulin secretion in the pancreatic beta-cell","volume":"353","author":"Wiederkehr","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-94-007-2869-1_1","article-title":"The oxidative phosphorylation system in mammalian mitochondria","volume":"942","author":"Papa","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6754","DOI":"10.1038\/s41467-022-34095-x","article-title":"Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic beta-cells","volume":"13","author":"Haythorne","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/s41589-024-01571-y","article-title":"Mitochondrial ATP generation is more proteome efficient than glycolysis","volume":"20","author":"Shen","year":"2024","journal-title":"Nat. Chem. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/s41467-019-08441-5","article-title":"A genetically encoded single-wavelength sensor for imaging cytosolic and cell surface ATP","volume":"10","author":"Lobas","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yoshida, T., Kakizuka, A., and Imamura, H. (2016). BTeam, a Novel BRET-Based Biosensor for the Accurate Quantification of ATP Concentration Within Living Cells. Sci. Rep., 6.","DOI":"10.1038\/srep39618"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/nchembio.1060","article-title":"Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis","volume":"8","author":"Anastasiou","year":"2012","journal-title":"Nat. Chem. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nmeth.3179","article-title":"Directed evolution of APEX2 for electron microscopy and proximity labeling","volume":"12","author":"Lam","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1038\/s41467-019-10189-x","article-title":"Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic \u03b2-cells","volume":"10","author":"Haythorne","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1039\/D0CB00163E","article-title":"Advances in single-cell multi-omics profiling","volume":"2","author":"Bai","year":"2021","journal-title":"RSC Chem. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zaher, A., and Stephens, S.B. (2025). Breaking the Feedback Loop of Beta-Cell Failure: Insight into the Pancreatic Beta-Cell\u2019s ER-Mitochondria Redox Balance. Cells, 14.","DOI":"10.3390\/cells14060399"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1038\/nrm3013","article-title":"Mitochondrial fusion and fission in cell life and death","volume":"11","author":"Westermann","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41392-023-01547-9","article-title":"Mitochondrial dynamics in health and disease: Mechanisms and potential targets","volume":"8","author":"Chen","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Tseng, W.W., Chu, C.H., Lee, Y.J., Zhao, S., Chang, C., Ho, Y.P., and Wei, A.C. (2024). Metabolic regulation of mitochondrial morphologies in pancreatic beta cells: Coupling of bioenergetics and mitochondrial dynamics. Commun. Biol., 7.","DOI":"10.1038\/s42003-024-06955-3"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1128\/MCB.05603-11","article-title":"Mitochondrial fission contributes to mitochondrial dysfunction and insulin resistance in skeletal muscle","volume":"32","author":"Jheng","year":"2012","journal-title":"Mol. Cell. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.3748\/wjg.v19.i10.1572","article-title":"Mitofusin-2 ameliorates high-fat diet-induced insulin resistance in liver of rats","volume":"19","author":"Gan","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/sj.emboj.7601963","article-title":"Fission and selective fusion govern mitochondrial segregation and elimination by autophagy","volume":"27","author":"Twig","year":"2008","journal-title":"EMBO J."},{"key":"ref_31","first-page":"161","article-title":"Dynamin-related protein 1 is implicated in endoplasmic reticulum stress-induced pancreatic beta-cell apoptosis","volume":"28","author":"Peng","year":"2011","journal-title":"Int. J. Mol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.biocel.2008.08.031","article-title":"Dynamin-related protein 1 mediates high glucose induced pancreatic beta cell apoptosis","volume":"41","author":"Men","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e141138","DOI":"10.1172\/jci.insight.141138","article-title":"Mitophagy protects beta cells from inflammatory damage in diabetes","volume":"5","author":"Sidarala","year":"2020","journal-title":"JCI Insight"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3245","DOI":"10.1210\/en.2018-00445","article-title":"In Vivo Deletion of Beta-Cell Drp1 Impairs Insulin Secretion Without Affecting Islet Oxygen Consumption","volume":"159","author":"Hennings","year":"2018","journal-title":"Endocrinology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/cdd.2012.81","article-title":"The pathways of mitophagy for quality control and clearance of mitochondria","volume":"20","author":"Ashrafi","year":"2013","journal-title":"Cell Death Differ."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/s41556-018-0176-2","article-title":"Mechanisms of mitophagy in cellular homeostasis, physiology and pathology","volume":"20","author":"Palikaras","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/s41392-023-01503-7","article-title":"The mitophagy pathway and its implications in human diseases","volume":"8","author":"Wang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/ncb2012","article-title":"PINK1\/Parkin-mediated mitophagy is dependent on VDAC1 and p62\/SQSTM1","volume":"12","author":"Geisler","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3233\/JPD-160989","article-title":"PINK1, Parkin, and Mitochondrial Quality Control: What can we Learn about Parkinson\u2019s Disease Pathobiology?","volume":"7","author":"Truban","year":"2017","journal-title":"J. Parkinsons Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"265","DOI":"10.2337\/db17-0321","article-title":"Clec16a, Nrdp1, and USP8 Form a Ubiquitin-Dependent Tripartite Complex That Regulates Beta-Cell Mitophagy","volume":"67","author":"Pearson","year":"2018","journal-title":"Diabetes"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.cmet.2008.08.013","article-title":"Loss of autophagy diminishes pancreatic beta cell mass and function with resultant hyperglycemia","volume":"8","author":"Jung","year":"2008","journal-title":"Cell Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1210\/en.2017-03273","article-title":"Beta-Cell Autophagy in Diabetes Pathogenesis","volume":"159","author":"Marasco","year":"2018","journal-title":"Endocrinology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1126\/science.1244851","article-title":"Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells","volume":"343","author":"Kronke","year":"2014","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.2337\/db07-1781","article-title":"Mitochondrial networking protects beta-cells from nutrient-induced apoptosis","volume":"58","author":"Molina","year":"2009","journal-title":"Diabetes"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1210\/er.2007-0023","article-title":"Glucolipotoxicity: Fuel excess and beta-cell dysfunction","volume":"29","author":"Poitout","year":"2008","journal-title":"Endocr. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"eadf2034","DOI":"10.1126\/science.adf2034","article-title":"Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues","volume":"388","author":"Walker","year":"2025","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3475","DOI":"10.2337\/db15-0376","article-title":"Diabetes Susceptibility Genes Pdx1 and Clec16a Function in a Pathway Regulating Mitophagy in beta-Cells","volume":"64","author":"Soleimanpour","year":"2015","journal-title":"Diabetes"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.cmet.2007.06.001","article-title":"Transcriptional control of brown fat determination by PRDM16","volume":"6","author":"Seale","year":"2007","journal-title":"Cell Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.cmet.2006.04.002","article-title":"Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation","volume":"3","author":"Uldry","year":"2006","journal-title":"Cell Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.biochi.2022.03.013","article-title":"Regulation of mitochondrial function by forkhead transcription factors","volume":"198","author":"Jerome","year":"2022","journal-title":"Biochimie"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.cmet.2016.03.005","article-title":"ERRgamma Is Required for the Metabolic Maturation of Therapeutically Functional Glucose-Responsive beta Cells","volume":"23","author":"Yoshihara","year":"2016","journal-title":"Cell Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"563","DOI":"10.2337\/db07-0698","article-title":"Forkhead transcription factor FoxO1 in adipose tissue regulates energy storage and expenditure","volume":"57","author":"Nakae","year":"2008","journal-title":"Diabetes"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/jgh.12021","article-title":"Forkhead box class O transcription factors in liver function and disease","volume":"28","author":"Tikhanovich","year":"2013","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.molmet.2015.08.001","article-title":"PGC-1 coactivators in beta-cells regulate lipid metabolism and are essential for insulin secretion coupled to fatty acids","volume":"4","author":"Oropeza","year":"2015","journal-title":"Mol. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"102","DOI":"10.2337\/diabetes.52.1.102","article-title":"Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes","volume":"52","author":"Butler","year":"2003","journal-title":"Diabetes"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"8152","DOI":"10.1002\/jcp.27603","article-title":"Insulin resistance: Review of the underlying molecular mechanisms","volume":"234","author":"Yaribeygi","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.cmet.2009.07.002","article-title":"PDX1 deficiency causes mitochondrial dysfunction and defective insulin secretion through TFAM suppression","volume":"10","author":"Gauthier","year":"2009","journal-title":"Cell Metab."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7648","DOI":"10.1093\/nar\/gkz505","article-title":"Structural insights into dimethylation of 12S rRNA by TFB1M: Indispensable role in translation of mitochondrial genes and mitochondrial function","volume":"47","author":"Liu","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5733","DOI":"10.1093\/hmg\/ddu288","article-title":"Loss of TFB1M results in mitochondrial dysfunction that leads to impaired insulin secretion and diabetes","volume":"23","author":"Sharoyko","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1126\/science.1251102","article-title":"Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer","volume":"344","author":"Tran","year":"2014","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1096\/fj.14-253831","article-title":"Macrophage polarization phenotype regulates adiponectin receptor expression and adiponectin anti-inflammatory response","volume":"29","author":"Kim","year":"2015","journal-title":"FASEB J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.cmet.2010.12.007","article-title":"A common variant in TFB1M is associated with reduced insulin secretion and increased future risk of type 2 diabetes","volume":"13","author":"Koeck","year":"2011","journal-title":"Cell Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4288","DOI":"10.1038\/s41467-024-48647-w","article-title":"HNF4A and HNF1A exhibit tissue specific target gene regulation in pancreatic beta cells and hepatocytes","volume":"15","author":"Ng","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1126\/science.1164097","article-title":"ATP-citrate lyase links cellular metabolism to histone acetylation","volume":"324","author":"Wellen","year":"2009","journal-title":"Science"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s11892-011-0248-1","article-title":"Metabolic programming, epigenetics, and gestational diabetes mellitus","volume":"12","author":"Pinney","year":"2012","journal-title":"Curr. Diabetes Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1101\/gad.191056.112","article-title":"Inhibition of \u03b1-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors","volume":"26","author":"Xiao","year":"2012","journal-title":"Genes Dev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.cmet.2016.07.002","article-title":"\u03b1-Ketoglutarate Accelerates the Initial Differentiation of Primed Human Pluripotent Stem Cells","volume":"24","author":"TeSlaa","year":"2016","journal-title":"Cell Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.cmet.2015.06.023","article-title":"Hypoxia Induces Production of L-2-Hydroxyglutarate","volume":"22","author":"Intlekofer","year":"2015","journal-title":"Cell Metab."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1097\/01.GIM.0000117333.21213.17","article-title":"Mitochondrial ribosomal proteins: Candidate genes for mitochondrial disease","volume":"6","author":"Sylvester","year":"2004","journal-title":"Genet. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/s12276-022-00797-x","article-title":"Mitoribosome insufficiency in beta cells is associated with type 2 diabetes-like islet failure","volume":"54","author":"Hong","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1126\/science.aaa3872","article-title":"The complete structure of the 55S mammalian mitochondrial ribosome","volume":"348","author":"Greber","year":"2015","journal-title":"Science"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cmet.2012.06.012","article-title":"CRIF1 is essential for the synthesis and insertion of oxidative phosphorylation polypeptides in the mammalian mitochondrial membrane","volume":"16","author":"Kim","year":"2012","journal-title":"Cell Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.2337\/diabetes.54.6.1892","article-title":"Evidence that the mitochondrial leucyl tRNA synthetase (LARS2) gene represents a novel type 2 diabetes susceptibility gene","volume":"54","author":"Hansen","year":"2005","journal-title":"Diabetes"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s00125-009-1557-7","article-title":"Genetic association analysis of LARS2 with type 2 diabetes","volume":"53","author":"Reiling","year":"2010","journal-title":"Diabetologia"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/S0092-8674(01)00378-6","article-title":"Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes","volume":"105","author":"Zhang","year":"2001","journal-title":"Cell"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Bordone, L., Motta, M.C., Picard, F., Robinson, A., Jhala, U.S., Apfeld, J., McDonagh, T., Lemieux, M., McBurney, M., and Szilvasi, A. (2006). Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells. PLoS Biol., 4, Erratum in PLoS Biol. 2015, 13, e1002346.","DOI":"10.1371\/journal.pbio.1002346"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3211","DOI":"10.2337\/diabetes.51.11.3211","article-title":"Uncoupling protein 2 knockout mice have enhanced insulin secretory capacity after a high-fat diet","volume":"51","author":"Joseph","year":"2002","journal-title":"Diabetes"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1152\/ajpendo.00231.2003","article-title":"Uncoupling protein-2 polymorphisms in type 2 diabetes, obesity, and insulin secretion","volume":"286","author":"Wang","year":"2004","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1210\/jc.2004-1072","article-title":"The common -866G\/A polymorphism in the promoter region of the UCP-2 gene is associated with reduced risk of type 2 diabetes in Caucasians from Italy","volume":"90","author":"Bulotta","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"104603","DOI":"10.1016\/j.isci.2022.104603","article-title":"Uncoupling protein 2 and aldolase B impact insulin release by modulating mitochondrial function and Ca2+ release from the ER","volume":"25","author":"Inoue","year":"2022","journal-title":"iScience"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1073\/pnas.1317400111","article-title":"UCP2 transports C4 metabolites out of mitochondria, regulating glucose and glutamine oxidation","volume":"111","author":"Vozza","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/415096a","article-title":"Superoxide activates mitochondrial uncoupling proteins","volume":"415","author":"Echtay","year":"2002","journal-title":"Nature"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"39673","DOI":"10.1074\/jbc.M112.393538","article-title":"Glutathionylation state of uncoupling protein-2 and the control of glucose-stimulated insulin secretion","volume":"287","author":"Mailloux","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.2337\/db06-1601","article-title":"Reactive oxygen species as a signal in glucose-stimulated insulin secretion","volume":"56","author":"Pi","year":"2007","journal-title":"Diabetes"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"12057","DOI":"10.1073\/pnas.0710434105","article-title":"UCP2 is highly expressed in pancreatic alpha-cells and influences secretion and survival","volume":"105","author":"Diao","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nrm1592","article-title":"The mitochondrial uncoupling-protein homologues","volume":"6","author":"Krauss","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cmet.2006.04.010","article-title":"Genipin inhibits UCP2-mediated proton leak and acutely reverses obesity- and high glucose-induced beta cell dysfunction in isolated pancreatic islets","volume":"3","author":"Zhang","year":"2006","journal-title":"Cell Metab."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1210\/endo.143.4.8717","article-title":"Induction of uncoupling protein 2 mRNA in beta-cells is stimulated by oxidation of fatty acids but not by nutrient oversupply","volume":"143","author":"Li","year":"2002","journal-title":"Endocrinology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1210\/er.2002-0012","article-title":"Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): Transcriptional coactivator and metabolic regulator","volume":"24","author":"Puigserver","year":"2003","journal-title":"Endocr. Rev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1172\/JCI21889","article-title":"Multiple environmental and genetic factors influence skeletal muscle PGC-1alpha and PGC-1beta gene expression in twins","volume":"114","author":"Ling","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s00125-007-0916-5","article-title":"Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion","volume":"51","author":"Ling","year":"2008","journal-title":"Diabetologia"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1007\/s001250100032","article-title":"Mutation analysis of peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) and relationships of identified amino acid polymorphisms to Type II diabetes mellitus","volume":"44","author":"Ek","year":"2001","journal-title":"Diabetologia"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1007\/s00125-002-0783-z","article-title":"No association between the G482S polymorphism of the proliferator-activated receptor-gamma coactivator-1 (PGC-1) gene and Type II diabetes in French Caucasians","volume":"45","author":"Lacquemant","year":"2002","journal-title":"Diabetologia"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"895","DOI":"10.2337\/diabetes.52.3.895","article-title":"A Gly482Ser missense mutation in the peroxisome proliferator-activated receptor gamma coactivator-1 is associated with altered lipid oxidation and early insulin secretion in Pima Indians","volume":"52","author":"Muller","year":"2003","journal-title":"Diabetes"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.2337\/diabetes.53.5.1385","article-title":"Complex haplotypes of the PGC-1alpha gene are associated with carbohydrate metabolism and type 2 diabetes","volume":"53","author":"Oberkofler","year":"2004","journal-title":"Diabetes"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1111\/j.1464-5491.2005.01709.x","article-title":"Peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PGC-1alpha) gene polymorphisms and their relationship to Type 2 diabetes in Asian Indians","volume":"22","author":"Vimaleswaran","year":"2005","journal-title":"Diabet. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s00125-005-0130-2","article-title":"Meta-analysis of the Gly482Ser variant in PPARGC1A in type 2 diabetes and related phenotypes","volume":"49","author":"Barroso","year":"2006","journal-title":"Diabetologia"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1111\/j.1464-5491.2006.01949.x","article-title":"The Gly482Ser variant of the PPARGC1 gene is associated with Type 2 diabetes mellitus in northern Chinese, especially men","volume":"23","author":"Sun","year":"2006","journal-title":"Diabet. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/81649","article-title":"Impaired insulin secretion and beta-cell loss in tissue-specific knockout mice with mitochondrial diabetes","volume":"26","author":"Silva","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.molmet.2017.05.005","article-title":"Mitochondrial transcription factor B2 is essential for mitochondrial and cellular function in pancreatic beta-cells","volume":"6","author":"Nicholas","year":"2017","journal-title":"Mol. Metab."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1172\/JCI27794","article-title":"PGC-1 coactivators: Inducible regulators of energy metabolism in health and disease","volume":"116","author":"Finck","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1007\/s00125-005-1855-7","article-title":"Association between polymorphisms in the nuclear respiratory factor 1 gene and type 2 diabetes mellitus in the Korean population","volume":"48","author":"Cho","year":"2005","journal-title":"Diabetologia"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.cmet.2013.12.002","article-title":"Pdx1 maintains beta cell identity and function by repressing an alpha cell program","volume":"19","author":"Gao","year":"2014","journal-title":"Cell Metab."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"NS20180060","DOI":"10.1042\/NS20180060","article-title":"Role of frataxin protein deficiency and metabolic dysfunction in Friedreich ataxia, an autosomal recessive mitochondrial disease","volume":"2","author":"Clark","year":"2018","journal-title":"Neuronal Signal."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3488","DOI":"10.2337\/db13-0152","article-title":"Loss of prohibitin induces mitochondrial damages altering beta-cell function and survival and is responsible for gradual diabetes development","volume":"62","author":"Supale","year":"2013","journal-title":"Diabetes"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1038\/nsmb.2159","article-title":"The mitochondrial transcription and packaging factor Tfam imposes a U-turn on mitochondrial DNA","volume":"18","author":"Ngo","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1126\/science.1258026","article-title":"Structure of the large ribosomal subunit from human mitochondria","volume":"346","author":"Brown","year":"2014","journal-title":"Science"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nature10257","article-title":"Mitochondrial uncoupling protein 2 structure determined by NMR molecular fragment searching","volume":"476","author":"Berardi","year":"2011","journal-title":"Nature"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nature24645","article-title":"Structure of PINK1 in complex with its substrate ubiquitin","volume":"552","author":"Schubert","year":"2017","journal-title":"Nature"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/s41586-018-0224-x","article-title":"Mechanism of parkin activation by PINK1","volume":"559","author":"Gladkova","year":"2018","journal-title":"Nature"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2948","DOI":"10.1021\/bi060969l","article-title":"Structural basis for induced fit mechanisms in DNA recognition by the Pdx1 homeodomain","volume":"46","author":"Longo","year":"2007","journal-title":"Biochemistry"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.taap.2006.01.003","article-title":"Diabetes and mitochondrial function: Role of hyperglycemia and oxidative stress","volume":"212","author":"Rolo","year":"2006","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.metabol.2009.07.021","article-title":"Superoxide production by mitochondria of insulin-sensitive tissues: Mechanistic differences and effect of early diabetes","volume":"59","author":"Herlein","year":"2010","journal-title":"Metabolism"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.bbadis.2016.11.010","article-title":"Mitochondrial dysfunction and oxidative stress in metabolic disorders\u2014A step towards mitochondria based therapeutic strategies","volume":"1863","author":"Bhatti","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1210\/endo-127-4-1580","article-title":"A 48-hour lipid infusion in the rat time-dependently inhibits glucose-induced insulin secretion and B cell oxidation through a process likely coupled to fatty acid oxidation","volume":"127","author":"Sako","year":"1990","journal-title":"Endocrinology"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1210\/endo.133.1.8319569","article-title":"Chronic perifusion of rat islets with palmitate suppresses glucose-stimulated insulin release","volume":"133","author":"Elks","year":"1993","journal-title":"Endocrinology"},{"key":"ref_117","first-page":"1584","article-title":"Long term exposure to fatty acids and ketones inhibits B-cell functions in human pancreatic islets of Langerhans","volume":"80","author":"Zhou","year":"1995","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_118","first-page":"316","article-title":"The role of oxidative stress in the pathogenesis of type 2 diabetes: From molecular mechanism to clinical implication","volume":"2","author":"Chang","year":"2010","journal-title":"Am. J. Transl. Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"E910","DOI":"10.1152\/ajpendo.00339.2010","article-title":"ss-Cell-specific pyruvate dehydrogenase deficiency impairs glucose-stimulated insulin secretion","volume":"299","author":"Srinivasan","year":"2010","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"30010","DOI":"10.1074\/jbc.M202066200","article-title":"Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression","volume":"277","author":"Kaneto","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.freeradbiomed.2010.12.006","article-title":"Oxidative stress, insulin signaling, and diabetes","volume":"50","author":"Rains","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1210\/en.2007-0988","article-title":"Reactive oxygen species-mediated pancreatic beta-cell death is regulated by interactions between stress-activated protein kinases, p38 and c-Jun N-terminal kinase, and mitogen-activated protein kinase phosphatases","volume":"149","author":"Hou","year":"2008","journal-title":"Endocrinology"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.2337\/db12-1097","article-title":"In vivo JNK activation in pancreatic beta-cells leads to glucose intolerance caused by insulin resistance in pancreas","volume":"62","author":"Arevalo","year":"2013","journal-title":"Diabetes"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2896","DOI":"10.2337\/diabetes.52.12.2896","article-title":"Oxidative stress induces nucleo-cytoplasmic translocation of pancreatic transcription factor PDX-1 through activation of c-Jun NH(2)-terminal kinase","volume":"52","author":"Kawamori","year":"2003","journal-title":"Diabetes"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1074\/jbc.M109.006734","article-title":"Glucose regulates steady-state levels of PDX1 via the reciprocal actions of GSK3 and AKT kinases","volume":"285","author":"Humphrey","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1016\/j.cellsig.2005.03.020","article-title":"Synergistic activation of JNK\/SAPK induced by TNF-alpha and IFN-gamma: Apoptosis of pancreatic beta-cells via the p53 and ROS pathway","volume":"17","author":"Kim","year":"2005","journal-title":"Cell. Signal."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.2337\/diabetes.49.9.1468","article-title":"The c-Jun amino-terminal kinase pathway is preferentially activated by interleukin-1 and controls apoptosis in differentiating pancreatic beta-cells","volume":"49","author":"Ammendrup","year":"2000","journal-title":"Diabetes"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"693","DOI":"10.2337\/dbi22-0030","article-title":"KATP Channels and the Metabolic Regulation of Insulin Secretion in Health and Disease: The 2022 Banting Medal for Scientific Achievement Award Lecture","volume":"72","author":"Ashcroft","year":"2023","journal-title":"Diabetes"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"266","DOI":"10.3892\/etm.2020.9396","article-title":"Mitochondrial dysfunction and pancreatic islet beta-cell failure (Review)","volume":"20","author":"Sha","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Iheagwam, F.N., Joseph, A.J., Adedoyin, E.D., Iheagwam, O.T., and Ejoh, S.A. (2025). Mitochondrial Dysfunction in Diabetes: Shedding Light on a Widespread Oversight. Pathophysiology, 32.","DOI":"10.3390\/pathophysiology32010009"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1007\/s00125-008-1054-4","article-title":"Age-related decline in mitochondrial DNA copy number in isolated human pancreatic islets","volume":"51","author":"Cree","year":"2008","journal-title":"Diabetologia"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1111\/j.1432-1033.1995.231_c.x","article-title":"Peroxynitrite formed by simultaneous nitric oxide and superoxide generation causes cyclosporin-A-sensitive mitochondrial calcium efflux and depolarisation","volume":"234","author":"Packer","year":"1995","journal-title":"Eur. J. Biochem."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1007\/s40200-021-00799-y","article-title":"Dysregulation of nitric oxide synthases during early and late pathophysiological conditions of diabetes mellitus leads to amassing of microvascular impedement","volume":"20","author":"Suresh","year":"2021","journal-title":"J. Diabetes Metab. Disord."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Kim, Y.K., Sussel, L., and Davidson, H.W. (2021). Inherent Beta Cell Dysfunction Contributes to Autoimmune Susceptibility. Biomolecules, 11.","DOI":"10.3390\/biom11040512"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Wang, C.H., and Wei, Y.H. (2020). Roles of Mitochondrial Sirtuins in Mitochondrial Function, Redox Homeostasis, Insulin Resistance and Type 2 Diabetes. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155266"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/s41419-023-05708-0","article-title":"Iron metabolism and ferroptosis in type 2 diabetes mellitus and complications: Mechanisms and therapeutic opportunities","volume":"14","author":"Miao","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"102282","DOI":"10.1016\/j.ceca.2020.102282","article-title":"Control by Ca2+ of mitochondrial structure and function in pancreatic beta-cells","volume":"91","author":"Georgiadou","year":"2020","journal-title":"Cell Calcium"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.2337\/diabetes.51.2007.S37","article-title":"Beta-cell mitochondria and insulin secretion: Messenger role of nucleotides and metabolites","volume":"51","author":"Wollheim","year":"2002","journal-title":"Diabetes"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1530\/EJE-11-0282","article-title":"Decreased expression of genes involved in oxidative phosphorylation in human pancreatic islets from patients with type 2 diabetes","volume":"165","author":"Olsson","year":"2011","journal-title":"Eur. J. Endocrinol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.molmet.2017.05.014","article-title":"Transcribing beta-cell mitochondria in health and disease","volume":"6","author":"Mulder","year":"2017","journal-title":"Mol. Metab."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Moon, D.O. (2023). NADPH Dynamics: Linking Insulin Resistance and Beta-Cells Ferroptosis in Diabetes Mellitus. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010342"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1007\/s00125-010-1685-0","article-title":"Regulation of insulin secretion: Role of mitochondrial signalling","volume":"53","author":"Jitrapakdee","year":"2010","journal-title":"Diabetologia"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/cc6779","article-title":"Bench-to-bedside review: Mitochondrial injury, oxidative stress and apoptosis--there is nothing more practical than a good theory","volume":"12","author":"Bayir","year":"2008","journal-title":"Crit. Care"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1161\/CIRCRESAHA.112.265819","article-title":"Mitochondria and mitophagy: The yin and yang of cell death control","volume":"111","author":"Kubli","year":"2012","journal-title":"Circ. Res."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Varghese, S.S., and Dhawan, S. (2023). Senescence: A double-edged sword in beta-cell health and failure?. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1196460"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"7691","DOI":"10.18632\/aging.202593","article-title":"Beta cell aging and age-related diabetes","volume":"13","author":"Zhu","year":"2021","journal-title":"Aging"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"448","DOI":"10.2337\/db09-0129","article-title":"Molecular and metabolic evidence for mitochondrial defects associated with beta-cell dysfunction in a mouse model of type 2 diabetes","volume":"59","author":"Lu","year":"2010","journal-title":"Diabetes"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Carroll, D.T., Miller, A., Fuhr, J., Elsakr, J.M., Ricciardi, V., Del Bene, A.N., Stephens, S., Krystofiak, E., Lindsley, S.R., and Kirigiti, M. (2024). Analysis of beta-cell maturity and mitochondrial morphology in juvenile non-human primates exposed to maternal Western-style diet during development. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1417437"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1089\/ars.2017.7351","article-title":"Dual Role of Nitric Oxide in Regulating the Response of Beta Cells to DNA Damage","volume":"29","author":"Oleson","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"E912","DOI":"10.1152\/ajpendo.00461.2017","article-title":"NLRP3 inflammasome mediates oxidative stress-induced pancreatic islet dysfunction","volume":"315","author":"Sokolova","year":"2018","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.canlet.2018.01.034","article-title":"The NLRP3 inflammasome: Role in metabolic disorders and regulation by metabolic pathways","volume":"419","author":"Jiang","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2710","DOI":"10.2337\/db11-0132","article-title":"Beta-cell uncoupling protein 2 regulates reactive oxygen species production, which influences both insulin and glucagon secretion","volume":"60","author":"Sultan","year":"2011","journal-title":"Diabetes"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"101116","DOI":"10.1016\/j.isci.2020.101116","article-title":"NADPH and Glutathione Redox Link TCA Cycle Activity to Endoplasmic Reticulum Homeostasis","volume":"23","author":"Gansemer","year":"2020","journal-title":"iScience"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Primary Care Advisory Group, ElSayed, N., Baig, A., Balapattabi, K., Bradley, S., Capelson, R., D\u2019sOuza, J., Gonzalez, J., Haynes, A., and Kim, M. (2025). Standards of Care in Diabetes-2025 Abridged for Primary Care. Clin. Diabetes, 43, 182.","DOI":"10.2337\/figshare.28619984.v1"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"de Mara\u00f1\u00f3n, A.M., D\u00edaz-Pozo, P., Canet, F., D\u00edaz-Morales, N., Abad-Jim\u00e9nez, Z., L\u00f3pez-Dom\u00e8nech, S., Vezza, T., Apostolova, N., Morillas, C., and Rocha, M. (2022). Metformin modulates mitochondrial function and mitophagy in peripheral blood mononuclear cells from type 2 diabetic patients. Redox Biol., 53.","DOI":"10.1016\/j.redox.2022.102342"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1042\/bj3480607","article-title":"Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain","volume":"348","author":"Owen","year":"2000","journal-title":"Biochem. J."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s00125-011-2340-0","article-title":"Metformin-treated patients with type 2 diabetes have normal mitochondrial complex I respiration","volume":"55","author":"Larsen","year":"2012","journal-title":"Diabetologia"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1530\/EJE-15-0572","article-title":"Effects of metformin on mitochondrial function of leukocytes from polycystic ovary syndrome patients with insulin resistance","volume":"173","author":"Victor","year":"2015","journal-title":"Eur. J. Endocrinol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1007\/s00125-010-1692-1","article-title":"Ablation of AMP-activated protein kinase alpha1 and alpha2 from mouse pancreatic beta cells and RIP2.Cre neurons suppresses insulin release in vivo","volume":"53","author":"Sun","year":"2010","journal-title":"Diabetologia"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.2337\/db09-0600","article-title":"Glucose deprivation regulates KATP channel trafficking via AMP-activated protein kinase in pancreatic beta-cells","volume":"58","author":"Lim","year":"2009","journal-title":"Diabetes"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"52042","DOI":"10.1074\/jbc.M307800200","article-title":"5\u2019-AMP-activated protein kinase controls insulin-containing secretory vesicle dynamics","volume":"278","author":"Tsuboi","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"198","DOI":"10.4161\/isl.1.3.9608","article-title":"Control of insulin granule dynamics by AMPK dependent KLC1 phosphorylation","volume":"1","author":"McDonald","year":"2009","journal-title":"Islets"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"E1023","DOI":"10.1152\/ajpendo.00532.2003","article-title":"Metformin, but not leptin, regulates AMP-activated protein kinase in pancreatic islets: Impact on glucose-stimulated insulin secretion","volume":"286","author":"Leclerc","year":"2004","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1089\/ars.2016.6859","article-title":"Sirt3 Deficiency Increased the Vulnerability of Pancreatic Beta Cells to Oxidative Stress-Induced Dysfunction","volume":"27","author":"Zhou","year":"2017","journal-title":"Antioxid. Redox Signal."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/ggi.14513","article-title":"Effects of nicotinamide mononucleotide on older patients with diabetes and impaired physical performance: A prospective, placebo-controlled, double-blind study","volume":"23","author":"Akasaka","year":"2023","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"5703","DOI":"10.1210\/jc.2019-01081","article-title":"Effects of Nicotinamide Riboside on Endocrine Pancreatic Function and Incretin Hormones in Nondiabetic Men with Obesity","volume":"104","author":"Dollerup","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s11357-022-00705-1","article-title":"The efficacy and safety of \u03b2-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: A randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial","volume":"45","author":"Yi","year":"2023","journal-title":"Geroscience"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/s41392-021-00723-z","article-title":"Nicotinamide mononucleotide: A potential effective natural compound against insulin resistance","volume":"6","author":"Roos","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Chang, N., Li, J., Lin, S., Zhang, J., Zeng, W., Ma, G., and Wang, Y. (2024). Emerging roles of SIRT1 activator, SRT2104, in disease treatment. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-55923-8"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/nature10112","article-title":"MicroRNAs 103 and 107 regulate insulin sensitivity","volume":"474","author":"Trajkovski","year":"2011","journal-title":"Nature"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s00592-019-01430-6","article-title":"Circulating miR-103 family as potential biomarkers for type 2 diabetes through targeting CAV-1 and SFRP4","volume":"57","author":"Luo","year":"2020","journal-title":"Acta Diabetol."},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Krishnan, P., Branco, R.C.S., Weaver, S.A., Chang, G., Lee, C.C., Syed, F., and Evans-Molina, C. (2024). miR-146a-5p mediates inflammation-induced beta cell mitochondrial dysfunction and apoptosis. J. Biol. Chem., 300.","DOI":"10.1101\/2024.03.18.585543"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/s42255-019-0073-4","article-title":"The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans","volume":"1","author":"Andreux","year":"2019","journal-title":"Nat. Metab."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"100633","DOI":"10.1016\/j.xcrm.2022.100633","article-title":"Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults","volume":"3","author":"Singh","year":"2022","journal-title":"Cell Rep. Med."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1002\/stem.3134","article-title":"Optimizing beta cell function through mesenchymal stromal cell-mediated mitochondria transfer","volume":"38","author":"Rackham","year":"2020","journal-title":"Stem Cells"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1002\/sctm.20-0466","article-title":"Protecting islet functional viability using mesenchymal stromal cells","volume":"10","author":"Hubber","year":"2021","journal-title":"Stem Cells Transl. Med."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"e1445948","DOI":"10.1080\/19382014.2018.1445948","article-title":"An engineered cell sheet composed of human islets and human fibroblast, bone marrow-derived mesenchymal stem cells, or adipose-derived mesenchymal stem cells: An in vitro comparison study","volume":"10","author":"Imamura","year":"2018","journal-title":"Islets"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.3727\/096368912X637046","article-title":"Mesenchymal stem cells and islet cotransplantation in diabetic rats: Improved islet graft revascularization and function by human adipose tissue-derived stem cells preconditioned with natural molecules","volume":"21","author":"Cavallari","year":"2012","journal-title":"Cell Transplant."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1089\/ten.teb.2013.0537","article-title":"Three-dimensional aggregates of mesenchymal stem cells: Cellular mechanisms, biological properties, and applications","volume":"20","author":"Sart","year":"2014","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Lee, H.J., Chae, C.W., and Han, H.J. (2023). Enhancing the therapeutic efficacy of mesenchymal stem cell transplantation in diabetes: Amelioration of mitochondrial dysfunction-induced senescence. Biomed. Pharmacother., 168.","DOI":"10.1016\/j.biopha.2023.115759"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1186\/s13287-022-02941-w","article-title":"Mesenchymal stem cell transplantation in newly diagnosed type-1 diabetes patients: A phase I\/II randomized placebo-controlled clinical trial","volume":"13","author":"Izadi","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13287-015-0261-4","article-title":"Multipotent mesenchymal stromal cells from patients with newly diagnosed type 1 diabetes mellitus exhibit preserved in vitro and in vivo immunomodulatory properties","volume":"7","author":"Yaochite","year":"2016","journal-title":"Stem Cell Res. Ther."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13287-015-0017-1","article-title":"Therapeutic efficacy and biodistribution of allogeneic mesenchymal stem cells delivered by intrasplenic and intrapancreatic routes in streptozotocin-induced diabetic mice","volume":"6","author":"Yaochite","year":"2015","journal-title":"Stem Cell Res. Ther."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1042\/bj20021288","article-title":"Glucagon-like peptide-1 mobilizes intracellular Ca2+ and stimulates mitochondrial ATP synthesis in pancreatic MIN6 beta-cells","volume":"369","author":"Tsuboi","year":"2003","journal-title":"Biochem. J."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"216","DOI":"10.3803\/EnM.2015.30.2.216","article-title":"Glucagon-Like Peptide-1 Increases Mitochondrial Biogenesis and Function in INS-1 Rat Insulinoma Cells","volume":"30","author":"Kang","year":"2015","journal-title":"Endocrinol. Metab."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.cmet.2006.10.001","article-title":"GLP-1 receptor activation improves beta cell function and survival following induction of endoplasmic reticulum stress","volume":"4","author":"Yusta","year":"2006","journal-title":"Cell Metab."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/nm1259","article-title":"Control of mRNA translation preserves endoplasmic reticulum function in beta cells and maintains glucose homeostasis","volume":"11","author":"Scheuner","year":"2005","journal-title":"Nat. Med."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"4823","DOI":"10.1016\/j.jmb.2018.10.020","article-title":"Elamipretide Promotes Mitophagosome Formation and Prevents Its Reduction Induced by Nutrient Excess in INS1 beta-cells","volume":"430","author":"Petcherski","year":"2018","journal-title":"J. Mol. Biol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1042\/BCJ20190616","article-title":"MitoTimer-based high-content screen identifies two chemically-related benzothiophene derivatives that enhance basal mitophagy","volume":"477","author":"Cerqueira","year":"2020","journal-title":"Biochem. J."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1038\/nm.4132","article-title":"Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents","volume":"22","author":"Ryu","year":"2016","journal-title":"Nat. Med."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1038\/embor.2013.168","article-title":"Loss of iron triggers PINK1\/Parkin-independent mitophagy","volume":"14","author":"Allen","year":"2013","journal-title":"EMBO Rep."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1038\/nm.3699","article-title":"Niclosamide ethanolamine-induced mild mitochondrial uncoupling improves diabetic symptoms in mice","volume":"20","author":"Tao","year":"2014","journal-title":"Nat. Med."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.apsb.2018.07.010","article-title":"Mitochondrial uncoupler BAM15 inhibits artery constriction and potently activates AMPK in vascular smooth muscle cells","volume":"8","author":"Tai","year":"2018","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.2337\/dci22-0034","article-title":"Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)","volume":"45","author":"Davies","year":"2022","journal-title":"Diabetes Care"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-anchem-061020-111722","article-title":"Analysis of Mitochondria by Single-Organelle Resolution","volume":"15","author":"Harbauer","year":"2022","journal-title":"Annu. Rev. Anal. Chem."},{"key":"ref_196","doi-asserted-by":"crossref","unstructured":"Schneider, A., Kurz, S., Manske, K., Janas, M., Heikenwalder, M., Misgeld, T., Aichler, M., Weissmann, S.F., Zischka, H., and Knolle, P. (2019). Single organelle analysis to characterize mitochondrial function and crosstalk during viral infection. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-44922-9"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"10239","DOI":"10.1002\/anie.201603007","article-title":"Label-Free Analysis of Single Viruses with a Resolution Comparable to That of Electron Microscopy and the Throughput of Flow Cytometry","volume":"55","author":"Ma","year":"2016","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"Degtyarev, M., Reichelt, M., and Lin, K. (2014). Novel quantitative autophagy analysis by organelle flow cytometry after cell sonication. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087707"},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Wang, Z., Gurlo, T., Satin, L.S., Fraser, S.E., and Butler, P.C. (2025). Subcellular Compartmentalization of Glucose Mediated Insulin Secretion. Cells, 14.","DOI":"10.3390\/cells14030198"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.molcel.2015.01.018","article-title":"Limited mitochondrial permeabilization causes DNA damage and genomic instability in the absence of cell death","volume":"57","author":"Ichim","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/35004029","article-title":"The coordinate release of cytochrome c during apoptosis is rapid, complete and kinetically invariant","volume":"2","author":"Goldstein","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.devcel.2010.03.014","article-title":"Resistance to caspase-independent cell death requires persistence of intact mitochondria","volume":"18","author":"Tait","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"98","DOI":"10.2144\/000113610","article-title":"Mitochondrial membrane potential probes and the proton gradient: A practical usage guide","volume":"50","author":"Perry","year":"2011","journal-title":"Biotechniques"},{"key":"ref_204","doi-asserted-by":"crossref","unstructured":"Picard, M., Taivassalo, T., Ritchie, D., Wright, K.J., Thomas, M.M., Romestaing, C., and Hepple, R.T. (2011). Mitochondrial structure and function are disrupted by standard isolation methods. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018317"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"101822","DOI":"10.1016\/j.xpro.2022.101822","article-title":"Fluorescent pulse-chase labeling to monitor long-term mitochondrial degradation in primary hippocampal neurons","volume":"3","author":"Schneider","year":"2022","journal-title":"STAR Protoc."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.tcb.2018.02.009","article-title":"Endoplasmic Reticulum-Mitochondrial Contactology: Structure and Signaling Functions","volume":"28","author":"Csordas","year":"2018","journal-title":"Trends Cell Biol."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/s41467-025-55825-x","article-title":"Mitochondrial segmentation and function prediction in live-cell images with deep learning","volume":"16","author":"Ding","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/s41419-022-04906-6","article-title":"Mitochondrial autophagy: Molecular mechanisms and implications for cardiovascular disease","volume":"13","author":"Li","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/s41419-025-07936-y","article-title":"Mitochondrial quality control in diabetes mellitus and complications: Molecular mechanisms and therapeutic strategies","volume":"16","author":"Chen","year":"2025","journal-title":"Cell Death Dis."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1083\/jcb.200809125","article-title":"Parkin is recruited selectively to impaired mitochondria and promotes their autophagy","volume":"183","author":"Narendra","year":"2008","journal-title":"J. Cell Biol."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"11835","DOI":"10.1073\/pnas.0914569107","article-title":"Parkin overexpression selects against a deleterious mtDNA mutation in heteroplasmic cybrid cells","volume":"107","author":"Suen","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"e12410","DOI":"10.1002\/jev2.12410","article-title":"Transfer of inflammatory mitochondria via extracellular vesicles from M1 macrophages induces ferroptosis of pancreatic beta cells in acute pancreatitis","volume":"13","author":"Gao","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1083\/jcb.201702058","article-title":"Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals","volume":"216","author":"Quiros","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"36393","DOI":"10.1074\/jbc.M112.399600","article-title":"ATF4-dependent regulation of the JMJD3 gene during amino acid deprivation can be rescued in Atf4-deficient cells by inhibition of deacetylation","volume":"287","author":"Shan","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"e1672","DOI":"10.1038\/cddis.2015.49","article-title":"Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity","volume":"6","author":"Halliday","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"3285","DOI":"10.1074\/jbc.RA119.009699","article-title":"A dual druggable genome-wide siRNA and compound library screening approach identifies modulators of parkin recruitment to mitochondria","volume":"295","author":"Scott","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/s41573-021-00371-6","article-title":"PROTAC targeted protein degraders: The past is prologue","volume":"21","author":"Bekes","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41580-023-00650-7","article-title":"Mitochondrial proteome research: The road ahead","volume":"25","author":"Baker","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"796","DOI":"10.18632\/aging.100943","article-title":"Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers","volume":"8","author":"Cobb","year":"2016","journal-title":"Aging"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/nature01627","article-title":"Humanin peptide suppresses apoptosis by interfering with Bax activation","volume":"423","author":"Guo","year":"2003","journal-title":"Nature"},{"key":"ref_221","doi-asserted-by":"crossref","unstructured":"Muzumdar, R.H., Huffman, D.M., Atzmon, G., Buettner, C., Cobb, L.J., Fishman, S., Budagov, T., Cui, L., Einstein, F.H., and Poduval, A. (2009). Humanin: A novel central regulator of peripheral insulin action. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006334"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.metabol.2009.08.001","article-title":"The neurosurvival factor Humanin inhibits beta-cell apoptosis via signal transducer and activator of transcription 3 activation and delays and ameliorates diabetes in nonobese diabetic mice","volume":"59","author":"Hoang","year":"2010","journal-title":"Metabolism"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.cmet.2015.02.009","article-title":"The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance","volume":"21","author":"Lee","year":"2015","journal-title":"Cell Metab."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.cmet.2018.06.008","article-title":"The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress","volume":"28","author":"Kim","year":"2018","journal-title":"Cell Metab."},{"key":"ref_225","doi-asserted-by":"crossref","unstructured":"Ramanjaneya, M., Bettahi, I., Jerobin, J., Chandra, P., Abi Khalil, C., Skarulis, M., Atkin, S.L., and Abou-Samra, A.B. (2019). Mitochondrial-Derived Peptides Are Down Regulated in Diabetes Subjects. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00331"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/s41467-020-20790-0","article-title":"MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis","volume":"12","author":"Reynolds","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.18632\/aging.101463","article-title":"Mitochondrial peptides modulate mitochondrial function during cellular senescence","volume":"10","author":"Kim","year":"2018","journal-title":"Aging"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s00281-020-00813-0","article-title":"Mitochondria, immunosenescence and inflammaging: A role for mitokines?","volume":"42","author":"Conte","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"135","DOI":"10.4161\/isl.2.3.11815","article-title":"Pancreatic islet plasticity: Interspecies comparison of islet architecture and composition","volume":"2","author":"Steiner","year":"2010","journal-title":"Islets"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/nrendo.2016.147","article-title":"Impact of islet architecture on \u03b2-cell heterogeneity, plasticity and function","volume":"12","author":"Roscioni","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1016\/j.celrep.2018.02.032","article-title":"\u03b1 Cell Function and Gene Expression Are Compromised in Type 1 Diabetes","volume":"22","author":"Brissova","year":"2018","journal-title":"Cell Rep."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"111792","DOI":"10.1016\/j.celrep.2022.111792","article-title":"Restoring glutamate receptor signaling in pancreatic alpha cells rescues glucagon responses in type 1 diabetes","volume":"41","author":"Panzer","year":"2022","journal-title":"Cell Rep."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"412","DOI":"10.2337\/db07-1298","article-title":"Glucose and pharmacological modulators of ATP-sensitive K+ channels control [Ca2+]c by different mechanisms in isolated mouse alpha-cells","volume":"58","author":"Quoix","year":"2009","journal-title":"Diabetes"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1113\/JP274581","article-title":"\u03b4-cells and \u03b2-cells are electrically coupled and regulate \u03b1-cell activity via somatostatin","volume":"596","author":"Briant","year":"2018","journal-title":"J. Physiol."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"403","DOI":"10.2337\/db08-0792","article-title":"Somatostatin secreted by islet delta-cells fulfills multiple roles as a paracrine regulator of islet function","volume":"58","author":"King","year":"2009","journal-title":"Diabetes"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"3700","DOI":"10.1038\/s41467-019-11517-x","article-title":"Structural basis for delta cell paracrine regulation in pancreatic islets","volume":"10","author":"Arrojo","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1038\/cdd.2014.211","article-title":"Transfer of mitochondria via tunneling nanotubes rescues apoptotic PC12 cells","volume":"22","author":"Wang","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nature18928","article-title":"Transfer of mitochondria from astrocytes to neurons after stroke","volume":"535","author":"Hayakawa","year":"2016","journal-title":"Nature"},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature09663","article-title":"A role for mitochondria in NLRP3 inflammasome activation","volume":"469","author":"Zhou","year":"2011","journal-title":"Nature"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nmeth.2869","article-title":"Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry","volume":"11","author":"Giesen","year":"2014","journal-title":"Nat. Methods"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.cmet.2018.11.014","article-title":"A Map of Human Type 1 Diabetes Progression by Imaging Mass Cytometry","volume":"29","author":"Damond","year":"2019","journal-title":"Cell Metab."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1038\/s41592-022-01409-2","article-title":"Museum of spatial transcriptomics","volume":"19","author":"Moses","year":"2022","journal-title":"Nat. Methods"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"eaau5324","DOI":"10.1126\/science.aau5324","article-title":"Molecular, spatial, and functional single-cell profiling of the hypothalamic preoptic region","volume":"362","author":"Moffitt","year":"2018","journal-title":"Science"},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.cell.2015.06.067","article-title":"Clarifying Tissue Clearing","volume":"162","author":"Richardson","year":"2015","journal-title":"Cell"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1038\/s41467-020-15906-5","article-title":"Versatile whole-organ\/body staining and imaging based on electrolyte-gel properties of biological tissues","volume":"11","author":"Susaki","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_246","doi-asserted-by":"crossref","unstructured":"Ye, L., Wu, H., and Xu, W. (2020). Deletion of Bmal1 Impairs Pancreatic beta-Cell Function via Mitochondrial Signaling Pathway. Biomed. Res. Int., 2020.","DOI":"10.1155\/2020\/9803024"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1529\/biophysj.104.041749","article-title":"A mitochondrial oscillator dependent on reactive oxygen species","volume":"87","author":"Cortassa","year":"2004","journal-title":"Biophys. J."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/23\/1861\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T10:27:24Z","timestamp":1764152844000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/23\/1861"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,26]]},"references-count":247,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["cells14231861"],"URL":"https:\/\/doi.org\/10.3390\/cells14231861","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,26]]}}}