β-Cell Maturation and Identity in Health and Disease

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 beta -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 beta -cell mass by cell-replacement or regeneration approaches. Implementing novel therapies requires deciphering the developmental mechanisms that generate beta -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 beta -cells and define their functional identity. Furthermore, we discuss different routes by which beta -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 beta -cell populations that have lost their functional phenotype. Finally, we discuss the recent progress and remaining challenges facing the generation of functional mature beta -cells from stem cells for cell-replacement therapy for diabetes treatment.