Tuning to the right signal.

Pancreatic beta cells are clustered in islets of Langerhans together with alpha cells in an arrangement that facilitates the tight coordination of insulin and glucagon secretion at the source of their release. Other secretory cells, including somatostatin-secreting delta cells and pancreatic polypeptide cells, co-localise with alpha and beta cells in the islet and serve to modulate islet endocrine output. A multitude of non-secretory cell types, including endothelial cells, pericytes, stromal cells, glial cells and macrophages, complete the cellular make up of the islet, which is further enhanced by (para)sympathetic nerve terminals that impinge on the islets via neurotransmitters released in the islet microenvironment. While this islet architecture is relatively simple compared with the vast complexity of the central nervous system, the constellation of cell types united in the islet nevertheless provides a rich substrate for local paracrine and autocrine interactions that affect diverse aspects of islet physiology, ranging from the modulation of hormone secretion to the regulation of islet cell mass via proliferation and death. In this issue of Diabetologia (DOI: 10.1007/s00125-015-3552-5 ), Yang et al take the notion of rich crosstalk within the islet as their point of departure for a systematic evaluation of the beta cell-protective properties of an extensive panel of over 200 factors, with some surprising and highly interesting results, as discussed in this commentary.