Lorenzo, Petra I.Cobo-Vuilleumier, NadiaMartín-Vázquez, EugeniaLópez-Noriega, LiviaGauthier, Benoit R.2022-05-302022-05-302021-04-19Lorenzo PI, Cobo-Vuilleumier N, Martín-Vázquez E, López-Noriega L, Gauthier BR. Harnessing the Endogenous Plasticity of Pancreatic Islets: A Feasible Regenerative Medicine Therapy for Diabetes? Int J Mol Sci. 2021 Apr 19;22(8):4239.http://hdl.handle.net/10668/3670Diabetes is a chronic metabolic disease caused by an absolute or relative deficiency in functional pancreatic β-cells that leads to defective control of blood glucose. Current treatments for diabetes, despite their great beneficial effects on clinical symptoms, are not curative treatments, leading to a chronic dependence on insulin throughout life that does not prevent the secondary complications associated with diabetes. The overwhelming increase in DM incidence has led to a search for novel antidiabetic therapies aiming at the regeneration of the lost functional β-cells to allow the re-establishment of the endogenous glucose homeostasis. Here we review several aspects that must be considered for the development of novel and successful regenerative therapies for diabetes: first, the need to maintain the heterogeneity of islet β-cells with several subpopulations of β-cells characterized by different transcriptomic profiles correlating with differences in functionality and in resistance/behavior under stress conditions; second, the existence of an intrinsic islet plasticity that allows stimulus-mediated transcriptome alterations that trigger the transdifferentiation of islet non-β-cells into β-cells; and finally, the possibility of using agents that promote a fully functional/mature β-cell phenotype to reduce and reverse the process of dedifferentiation of β-cells during diabetes.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/DiabetesRegenerationβ-cell heterogeneityTransdifferentiationRedifferentiationSinglecell transcriptomicsPAX4LRH-1/NR52AHMG20ADiabetes mellitusRegeneraciónTransdiferenciaciónCélulas secretoras de insulinaHomeostasisMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell TransdifferentiationMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 1Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Pancreatic Hormones::InsulinsMedical Subject Headings::Disciplines and Occupations::Health Occupations::Medicine::Regenerative MedicineMedical Subject Headings::Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucose::Blood GlucoseMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Transcription, Genetic::TranscriptomeMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell TransdifferentiationMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Hypoglycemic AgentsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::PhenotypeMedical Subject Headings::Anatomy::Endocrine System::Enteroendocrine Cells::Insulin-Secreting Cellsreview article33921851Acceso abierto10.3390/ijms220842391422-0067PMC8073058