Pancreatic β-cell heterogeneity in health and diabetes: classes, sources, and subtypes

Pancreatic β-cells perform glucose-stimulated insulin secretion, a process at the center of type 2 diabetes etiology. Efforts to understand how β-cells behave in healthy and stressful conditions have revealed a wide degree of morphological, functional, and transcriptional heterogeneity. Sources of heterogeneity include β-cell topography, developmental origin, maturation state, and stress response. Advances in sequencing and imaging technologies have led to the identification of β-cell subtypes, which play distinct roles in the islet niche. This review examines β-cell heterogeneity from morphological, functional, and transcriptional perspectives, and considers the relevance of topography, maturation, development, and stress response. It also discusses how these factors have been used to identify β-cell subtypes, and how heterogeneity is impacted by diabetes. We examine open questions in the field and discuss recent technological innovations that could advance understanding of β-cell heterogeneity in health and disease.