The maintenance of glucose homeostasis is fundamental for survival and health. Diabetes develops when glucose homeostasis fails. Type 2 diabetes (T2D) is characterized by insulin resistance and pancreatic β-cell failure. The failure of β-cells to compensate for insulin resistance results in hyperglycemia, which in turn drives altered lipid metabolism and β-cell failure. Thus, insulin secretion by pancreatic β-cells is a primary component of glucose homeostasis. Impaired β-cell function and reduced β-cell mass are found in diabetes. Both features stem from a failure to maintain β-cell identity, which causes β-cells to dedifferentiate into nonfunctional endocrine progenitor-like cells or to trans-differentiate into other endocrine cell types. In this regard, one of the key issues in achieving disease modification is how to reestablish β-cell identity. In this review, we focus on the causes and implications of β-cell failure, as well as its potential reversibility as a T2D treatment.
© 2023. The Author(s).