Ephs and Ephrins Keep Pancreatic β Cells Connected

The regulation of metabolic processes requires that cells communicate with their neighbors to ensure an appropriate response to the changing environment. The pancreas is a classic example of a tissue that depends on intercellular communication among the same (autocrine) and/or different (paracrine) cell types. The human pancreas is composed of over a million islets, each islet comprising several thousand cells including primarily insulin-secreting β cells but also glucagon-secreting α cells, somatostatin-secreting δ cells, pancreatic polypeptide-secreting (PP) cells, and ghrelin-producing ε cells. Within each islet, the different endocrine cells are thought to communicate with each other, either extracellularly via secreted products or directly through cell junctions. A role for paracrine and autocrine communication in the regulation of islet secretory function was proposed decades ago (Halban et al., 1982). For instance, insulin release from β cells can act on α cells to influence glucagon secretion, and somatostatin from δ cells acts as a paracrine inhibitor of neighboring α and β cells (Bonner-Weir and Orci, 1982; Samols and Stagner, 1990). Although intercellular exchange between β cells through membrane channels was confirmed by electrophysiologic and metabolic coupling experiments, the proteins and signaling mechanisms that underlie the communication between these insulin-secreting cells remain unclear. In this issue, Konstantinova et al. (2007) reveal that signaling via an ephrin ligand and its Eph receptor mediate communication between β cells.