Talchai C, Xuan S, Lin HV, Sussel L, Accili D (2012) Pancreatic β cell dedifferentiation as a mechanism of diabetic β cell failure. Cell 150(6):1223–1234. https://doi.org/10.1016/j.cell.2012.07.029

Article  CAS  PubMed  PubMed Central  Google Scholar 

Remedi MS, Emfinger C (2016) Pancreatic β-cell identity in diabetes. Diabetes Obes Metab 18(Suppl 1):110–116. https://doi.org/10.1111/dom.12727

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang J, Liu F (2020) The de-, re-, and trans-differentiation of β-cells: regulation and function. Semin Cell Dev Biol 103:68–75. https://doi.org/10.1016/j.semcdb.2020.01.003

Article  PubMed  Google Scholar 

Cigliola V, Thorel F, Chera S, Herrera PL (2016) Stress-induced adaptive islet cell identity changes. Diabetes Obes Metab 18(Suppl 1):87–96. https://doi.org/10.1111/dom.12726

Article  CAS  PubMed  PubMed Central  Google Scholar 

Amo-Shiinoki K, Tanabe K, Hoshii Y et al (2021) Islet cell dedifferentiation is a pathologic mechanism of long-standing progression of type 2 diabetes. JCI insight 6(1):e143791. https://doi.org/10.1172/jci.insight.143791

Article  PubMed  PubMed Central  Google Scholar 

Wang Z, York NW, Nichols CG, Remedi MS (2014) Pancreatic β cell dedifferentiation in diabetes and redifferentiation following insulin therapy. Cell Metab 19(5):872–882. https://doi.org/10.1016/j.cmet.2014.03.010

Article  CAS  PubMed  PubMed Central  Google Scholar 

Son J, Accili D (2023) Reversing pancreatic β-cell dedifferentiation in the treatment of type 2 diabetes. Exp Mol Med 55(8):1652–1658. https://doi.org/10.1038/s12276-023-01043-8

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lemaire K, Thorrez L, Schuit F (2016) Disallowed and allowed gene expression: two faces of mature islet beta cells. Annu Rev Nutr 36:45–71. https://doi.org/10.1146/annurev-nutr-071715-050808

Article  CAS  PubMed  Google Scholar 

Sekine N, Cirulli V, Regazzi R et al (1994) Low lactate dehydrogenase and high mitochondrial glycerol phosphate dehydrogenase in pancreatic beta-cells. Potential role in nutrient sensing. J Biol Chem 269(7):4895–4902

Article  CAS  PubMed  Google Scholar 

Rutter GA, Sidarala V, Kaufman BA, Soleimanpour SA (2023) Mitochondrial metabolism and dynamics in pancreatic beta cell glucose sensing. Biochem J 480(11):773–789. https://doi.org/10.1042/bcj20230167

Article  CAS  PubMed  Google Scholar 

Cuozzo F, Viloria K, Shilleh AH et al (2024) LDHB contributes to the regulation of lactate levels and basal insulin secretion in human pancreatic β cells. Cell Rep 43(4):114047. https://doi.org/10.1016/j.celrep.2024.114047

Article  CAS  PubMed  PubMed Central  Google Scholar 

Haythorne E, Lloyd M, Walsby-Tickle J et al (2022) Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells. Nat Commun 13(1):6754. https://doi.org/10.1038/s41467-022-34095-x

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li X, Zhang L, Meshinchi S et al (2006) Islet microvasculature in islet hyperplasia and failure in a model of type 2 diabetes. Diabetes 55(11):2965–2973. https://doi.org/10.2337/db06-0733

Article  CAS  PubMed  Google Scholar 

Hou J, Li Z, Zhong W et al (2017) Temporal transcriptomic and proteomic landscapes of deteriorating pancreatic islets in type 2 diabetic rats. Diabetes 66(8):2188–2200. https://doi.org/10.2337/db16-1305

Article  CAS  PubMed  Google Scholar 

Montemurro C, Nomoto H, Pei L et al (2019) IAPP toxicity activates HIF1α/PFKFB3 signaling delaying β-cell loss at the expense of β-cell function. Nat Commun 10(1):2679. https://doi.org/10.1038/s41467-019-10444-1

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sacco F, Seelig A, Humphrey SJ et al (2019) Phosphoproteomics reveals the GSK3–PDX1 axis as a key pathogenic signaling node in diabetic islets. Cell Metab 29(6):1422-1432.e1423. https://doi.org/10.1016/j.cmet.2019.02.012

Article  CAS  PubMed  Google Scholar 

Ilegems E, Bryzgalova G, Correia J et al (2022) HIF-1α inhibitor PX-478 preserves pancreatic β cell function in diabetes. Sci Transl Med 14(638):eaba9112. https://doi.org/10.1126/scitranslmed.aba9112

Article  CAS  PubMed  Google Scholar 

Chen X, Wang Y, Wang JN et al (2024) Lactylation-driven FTO targets CDK2 to aggravate microvascular anomalies in diabetic retinopathy. EMBO Mol Med 16(2):294–318. https://doi.org/10.1038/s44321-024-00025-1

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ma XM, Geng K, Wang P, Jiang Z, Law BY, Xu Y (2024) MCT4-dependent lactate transport: a novel mechanism for cardiac energy metabolism injury and inflammation in type 2 diabetes mellitus. Cardiovasc Diabetol 23(1):96. https://doi.org/10.1186/s12933-024-02178-2

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang X, Chen J, Lin R et al (2024) Lactate drives epithelial–mesenchymal transition in diabetic kidney disease via the H3K14la/KLF5 pathway. Redox Biol 75:103246. https://doi.org/10.1016/j.redox.2024.103246

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sun X, Wang L, Obayomi SMB, Wei Z (2021) Epigenetic regulation of β cell identity and dysfunction. Front Endocrinol 12:725131. https://doi.org/10.3389/fendo.2021.725131

Article  Google Scholar 

Osipovich AB, Stancill JS, Cartailler JP, Dudek KD, Magnuson MA (2020) Excitotoxicity and overnutrition additively impair metabolic function and identity of pancreatic β-cells. Diabetes 69(7):1476–1491. https://doi.org/10.2337/db19-1145

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li Y, Cao Q, Hu Y et al (2024) Advances in the interaction of glycolytic reprogramming with lactylation. Biomed Pharmacother 177:116982. https://doi.org/10.1016/j.biopha.2024.116982

Article  CAS  PubMed  Google Scholar 

Hu Y, He Z, Li Z et al (2024) Lactylation: the novel histone modification influence on gene expression, protein function, and disease. Clin Epigenet 16(1):72. https://doi.org/10.1186/s13148-024-01682-2

Article  CAS  Google Scholar 

Lin Y, Bai M, Wang S et al (2022) Lactate is a key mediator that links obesity to insulin resistance via modulating cytokine production from adipose tissue. Diabetes 71(4):637–652. https://doi.org/10.2337/db21-0535

Article  CAS  PubMed  Google Scholar 

Nomoto H, Pei L, Montemurro C et al (2020) Activation of the HIF1α/PFKFB3 stress response pathway in beta cells in type 1 diabetes. Diabetologia 63(1):149–161. https://doi.org/10.1007/s00125-019-05030-5

Article  CAS  PubMed  Google Scholar 

Fu Q, Qian Y, Jiang H et al (2024) Genetic lineage tracing identifies adaptive mechanisms of pancreatic islet β cells in various mouse models of diabetes with distinct age of initiation. Sci China Life Sci 67(3):504–517. https://doi.org/10.1007/s11427-022-2372-y

Article  CAS  PubMed