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Volume 22
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Review

Harnessing the Endogenous Plasticity of Pancreatic Islets: A Feasible Regenerative Medicine Therapy for Diabetes?

by
Petra I. Lorenzo
1,*,
Nadia Cobo-Vuilleumier
1,
Eugenia Martín-Vázquez
1,
Livia López-Noriega
1 and
Benoit R. Gauthier
1,2,*
1
Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucía-University of Pablo de Olavide-University of Seville-CSIC, 41092 Seville, Spain
2
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 028029 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(8), 4239; https://doi.org/10.3390/ijms22084239
Submission received: 18 March 2021 / Revised: 16 April 2021 / Accepted: 16 April 2021 / Published: 19 April 2021
(This article belongs to the Collection Feature Papers in Molecular Genetics and Genomics)
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Abstract

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.
Keywords: diabetes; regeneration; β-cell heterogeneity; transdifferentiation; redifferentiation; single-cell transcriptomics; PAX4; LRH-1/NR52A; HMG20A diabetes; regeneration; β-cell heterogeneity; transdifferentiation; redifferentiation; single-cell transcriptomics; PAX4; LRH-1/NR52A; HMG20A

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MDPI and ACS Style

Lorenzo, P.I.; Cobo-Vuilleumier, N.; Martín-Vázquez, E.; López-Noriega, L.; Gauthier, B.R. Harnessing the Endogenous Plasticity of Pancreatic Islets: A Feasible Regenerative Medicine Therapy for Diabetes? Int. J. Mol. Sci. 2021, 22, 4239. https://doi.org/10.3390/ijms22084239

AMA Style

Lorenzo 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? International Journal of Molecular Sciences. 2021; 22(8):4239. https://doi.org/10.3390/ijms22084239

Chicago/Turabian Style

Lorenzo, Petra I., Nadia Cobo-Vuilleumier, Eugenia Martín-Vázquez, Livia López-Noriega, and Benoit R. Gauthier. 2021. "Harnessing the Endogenous Plasticity of Pancreatic Islets: A Feasible Regenerative Medicine Therapy for Diabetes?" International Journal of Molecular Sciences 22, no. 8: 4239. https://doi.org/10.3390/ijms22084239

APA Style

Lorenzo, P. I., Cobo-Vuilleumier, N., Martín-Vázquez, E., López-Noriega, L., & Gauthier, B. R. (2021). Harnessing the Endogenous Plasticity of Pancreatic Islets: A Feasible Regenerative Medicine Therapy for Diabetes? International Journal of Molecular Sciences, 22(8), 4239. https://doi.org/10.3390/ijms22084239

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