Quo vadis: Where have the β-cells gone?

Abstract

Islets of Langerhans are a central player for the maintenance of glucose homeostasis in the body. In the case of insulin resistance, large insulin secretion is required by augmenting the functional capacity of single β-cells or increasing the number of insulin-secreting cells. While such compensatory mechanisms for the protection of glucose homeostasis operate in non-diabetic subjects, β-cell inadequacy for insulin resistance represents a key feature in the pathogenesis of type 2 diabetes. Studies in non-diabetic subjects disclosed that the number and mass of β-cells increase in response to an increase in body mass index1. One might wonder, then, where the new β-cells come from, and how they develop. Efforts to clarify such issues have been hampered, however, as a result of the difficulty of the use of human materials that do not allow longitudinal studies or guarantee of the sample quality for analysis of accurate metabolic and hormonal profiling. By overcoming this difficulty, recent studies by Mezza et al.2 from Harvard proposed two pathways as a source of new β-cells for compensation: neogenesis from duct cells and transdifferentiation of α-cells to β-cells (Figure​(Figure11).