The higher organization of β-cells into spheroid structures termed islets of Langerhans is critical for the proper regulation of insulin secretion. Thus, rodent β-cells form a functional syncytium that integrates and propagates information encoded by secretagogues, producing a "gain-of-function" in hormone release through the generation of coordinated cell-cell activity. By contrast, human islets possess divergent topology, and this may have repercussions for the cell-cell communication pathways that mediate the population dynamics underlying the intraislet regulation of insulin secretion. This is pertinent for type 2 diabetes mellitus pathogenesis, and its study in rodent models, because environmental and genetic factors may converge on these processes in a species-specific manner to precipitate the defective insulin secretion associated with glucose intolerance. The aim of the present minireview is therefore to discuss the structural and functional underpinnings that influence insulin secretion from human islets, and the possibility that dyscoordination between individual β-cells may play an important role in some forms of type 2 diabetes mellitus.