Human islets contain four distinct subtypes of β cells

Human pancreatic islets of Langerhans contain five distinct endocrine cell types, each producing a characteristic hormone. The dysfunction or loss of the insulin-producing beta cells causes diabetes mellitus, a disease that harms millions. Until now, beta cells were generally regarded as a single, homogenous cell population. Here we identify four antigenically distinct subtypes of human beta cells, which we refer to as beta 1-4, and which are distinguished by differential expression of ST8SIA1 and CD9. These subpopulations are always present in normal adult islets and have diverse gene expression profiles and distinct basal and glucose-stimulated insulin secretion. Importantly, the beta cell subtype distribution is profoundly altered in type 2 diabetes. These data suggest that this antigenically defined beta cell heterogeneity is functionally and likely medically relevant.