The De-, Re-, and trans-differentiation of β-cells: Regulation and function

Diabetes is a serious, costly, and major health problem worldwide. Whereas diabetes could be alleviated by medication, this disease could not be fully cured at the present time due to the lack of effective therapeutic treatment for β-cell loss and/or dysfunction. Increased β-cell mass or volume could be achieved via differentiation of embryonic stem (ES) cells or pluripotent stem cells or through β-cell renewal, including proliferation, redifferentiation, and transdifferentiation. Data cumulated over the past several years suggest that increased β-cell dedifferentiation plays a crucial role in the progression of diabetes, shedding new light on potential targets for β-cell replacement therapy. In this review, we summarize current views on β-cell dedifferentiation, redifferentiation, and transdifferentiation. We also discuss potential mechanisms regulating these key processes to maintain β-cell homeostasis. Understanding pancreatic β-cell differentiation and dedifferentiation could be provide important information on developing effective strategies to cure diabetes.