RESUMEN
Human pancreatic islets of Langerhans contain five distinct endocrine cell types, each producing a characteristic hormone. The dysfunction or loss of the insulin-producing ß cells causes diabetes mellitus, a disease that harms millions. Until now, ß cells were generally regarded as a single, homogenous cell population. Here we identify four antigenically distinct subtypes of human ß cells, which we refer to as ß1-4, 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 ß cell subtype distribution is profoundly altered in type 2 diabetes. These data suggest that this antigenically defined ß cell heterogeneity is functionally and likely medically relevant.
Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Células Secretoras de Insulina/citología , Sialiltransferasas/metabolismo , Tetraspanina 29/metabolismo , Adulto , Anciano , Femenino , Citometría de Flujo , Hemoglobina Glucada/metabolismo , Humanos , Células Secretoras de Insulina/metabolismo , Islotes Pancreáticos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
RNA editing has a major impact on the genes and genomes that it modifies. Editing by insertion, deletion and base conversion exists in nuclear, mitochondrial and viral genomes throughout the eukaryotic lineage. Editing was first discovered in kinetoplastids, and recent work has resulted in the characterization of some components of the editing machinery. Two proteins with ligase activity have been identified in Trypanosoma brucei, and other proteins in the editosome complex are yielding to the probe of research. A second group of protists, myxomycetes, are unique in their use of four different types of editing within a single transcript. Phylogenetic analysis of editing in representative myxomycetes revealed a different history of the four types of editing in this lineage. Development of a soluble in vitro editing system has provided further support for the co-transcriptional nature of editing in Physarum polycephalum, and will certainly provide future opportunities for understanding this mysterious process.