Harnessing the endogenous plasticity of pancreatic islets: A feasible regenerative medicine therapy for diabetes?

Autor: Lorenzo, Petra I., Cobo-Vuilleumier, Nadia, Martín-Vázquez, Eugenia, López-Noriega, Livia, Gauthier, Benoit R.
Přispěvatelé: Junta de Andalucía, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, European Commission, Juvenile Diabetes Research Foundation, Fundación Vencer el Cancer, Asociación Lucha y Sonríe por la Vida (España), Fundación DiabetesCERO, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), [Lorenzo,PI, Cobo-Vuilleumier,N, Martín-Vázquez,E, López-Noriega,L, Gauthier,BR] Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucía-University of Pablo de Olavide-University of Seville-CSIC, Seville, Spain. [Gauthier,BR] Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain., Authors were/are funded by grants from Consejería de Salud, Fundación Pública Andaluza Progreso y Salud, Junta de Andalucía (PI-0727-2010, December 2010 to B.R.G., PI-0085-2013, December 2013 to P.I.L., and PI-0001-2020, December 2020 to B.R.G. and P.I.L.), Consejería de Economía, Innovación y Ciencia, Junta de Andalucía (P10-CTS-6359 to B.R.G.), Ministerio de Economía y Competitividad, Instituto de Salud Carlos III, cofunded by Fondos FEDER (PI10/00871, January 2011 and PI13/00593, January 2014 to B.R.G.), Ministerio de Economía y Competitividad, Plan Nacional (BFU2017-83588-P, January 2018 to B.R.G. and PRE2018-084907, January 2018 to E.M.-V.), Juvenile Diabetes Research Foundation JDRF (17-2013-372, August 2013 and 2-SRA-2019-837-S-B, August 2019 to B.R.G:), and Fundacion Vencer el Cancer (to B.R.G.). Special thanks to ALUSVI (Asociación Lucha y Sonríe por la Vida, Pilas), a local Andalusian association, and the Fundacion DiabetesCero for their unconditional financial support.
Rok vydání: 2021
Předmět:
Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings]
Redifferentiation
LRH-1/NR52A
Regeneración
Transdiferenciación
Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus
Type 1 [Medical Subject Headings]
Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings]
Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Transcription
Genetic::Transcriptome [Medical Subject Headings]
Diabetes mellitus
Células secretoras de insulina
Organisms::Eukaryota::Animals [Medical Subject Headings]
Homeostasis
Regeneration
Anatomy::Endocrine System::Enteroendocrine Cells::Insulin-Secreting Cells [Medical Subject Headings]
Chemicals and Drugs::Hormones
Hormone Substitutes
and Hormone Antagonists::Hormones::Peptide Hormones::Pancreatic Hormones::Insulins [Medical Subject Headings]
Transdifferentiation
PAX4
Diabetes
β-cell heterogeneity
Singlecell transcriptomics
Disciplines and Occupations::Health Occupations::Medicine::Regenerative Medicine [Medical Subject Headings]
Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Hypoglycemic Agents [Medical Subject Headings]
HMG20A
Single-cell transcriptomics
Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Transdifferentiation [Medical Subject Headings]
Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucose::Blood Glucose [Medical Subject Headings]
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
Popis: Diabetes 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. Authors were/are funded by grants from Consejería de Salud, Fundación Pública Andaluza Progreso y Salud, Junta de Andalucía (PI-0727-2010, December 2010 to B.R.G., PI-0085-2013, December 2013 to P.I.L., and PI-0001-2020, December 2020 to B.R.G. and P.I.L.); Consejería de Economía, Innovación y Ciencia, Junta de Andalucía (P10-CTS-6359 to B.R.G.); Ministerio de Economía y Competitividad, Instituto de Salud Carlos III, cofunded by Fondos FEDER (PI10/00871, January 2011 and PI13/00593, January 2014 to B.R.G.); Ministerio de Economía y Competitividad, Plan Nacional (BFU2017-83588-P, January 2018 to B.R.G. and PRE2018-084907, January 2018 to E.M.-V.); Juvenile Diabetes Research Foundation JDRF (17-2013-372, August 2013 and 2-SRA-2019-837-S-B, August 2019 to B.R.G:); and Fundacion Vencer el Cancer (to B.R.G.). Special thanks to ALUSVI (Asociación Lucha y Sonríe por la Vida, Pilas), a local Andalusian association, and the Fundacion DiabetesCero for their unconditional financial support.
Databáze: OpenAIRE
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