β-Cells are not uniform after all-Novel insights into molecular heterogeneity of insulin-secreting cells.

While the β-cells of the endocrine pancreas are defined as cells with high levels of insulin production and tight stimulus-secretion coupling, the existence of functional heterogeneity among them has been known for decades. Recent advances in molecular technologies, in particular single-cell profiling on both the protein and messenger RNA level, have uncovered that β-cells exist in several antigenically and molecularly definable states. Using antibodies to cell surface markers or multidimensional clustering of β-cells using more than 20 protein markers by mass cytometry, 4 distinct groups of β-cells could be differentiated. However, whether these states represent permanent cell lineages or are readily interconvertible from one group to another remains to be determined. Nevertheless, future analysis of the pathogenesis of type 1 and type 2 diabetes will certainly benefit from a growing appreciation of β-cell heterogeneity. Here, we aim to summarize concisely the recent advances in the field and their possible impact on our understanding of β-cell physiology and pathophysiology.