New Understanding of β-Cell Heterogeneity and In Situ Islet Function

Insulin secreting β-cells are heterogeneous in their regulation of hormone release. While long known, recent technological advances and new markers have allowed the identification of novel subpopulations, improving our understanding of the molecular basis for heterogeneity. This includes specific sub-populations with distinct functional characteristics, developmental programs, abilities to proliferate in response to metabolic or developmental cues, and resistance to immune-mediated damage. Importantly, these sub-populations change in disease or in aging, including in human disease. While discovering new β-cell subpopulations has substantially advanced our understanding of islet biology, a point of caution is that these characteristics have often necessarily been identified in single β-cells dissociated from the islet. β-cells in the islet show extensive communication with each other via gap junctions, and with other cell types via diffusible chemical messengers. As such, how these different sub-populations contribute to in-situ islet function, including during plasticity, is not well understood. We will discuss recent findings revealing functional β-cell subpopulations in the intact islet, the underlying basis for these identified sub-populations, and how these sub-populations may influence in-situ islet function. Furthermore, we will discuss the outlook for emerging technologies to gain further insight into the role of sub-populations in in-situ islet function.