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ß-Cell Maturation and Identity in Health and Disease.

Salinno, Ciro; Cota, Perla; Bastidas-Ponce, Aimée; Tarquis-Medina, Marta; Lickert, Heiko; Bakhti, Mostafa.
Int J Mol Sci; 20(21)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31671683
The exponential increase of patients with diabetes mellitus urges for novel therapeutic strategies to reduce the socioeconomic burden of this disease. The loss or dysfunction of insulin-producing ß-cells, in patients with type 1 and type 2 diabetes respectively, put these cells at the center of the disease initiation and progression. Therefore, major efforts have been taken to restore the ß-cell mass by cell-replacement or regeneration approaches. Implementing novel therapies requires deciphering the developmental mechanisms that generate ß-cells and determine the acquisition of their physiological phenotype. In this review, we summarize the current understanding of the mechanisms that coordinate the postnatal maturation of ß-cells and define their functional identity. Furthermore, we discuss different routes by which ß-cells lose their features and functionality in type 1 and 2 diabetic conditions. We then focus on potential mechanisms to restore the functionality of those ß-cell populations that have lost their functional phenotype. Finally, we discuss the recent progress and remaining challenges facing the generation of functional mature ß-cells from stem cells for cell-replacement therapy for diabetes treatment.