The islets of Langerhans collectively form the endocrine pancreas, the organ that is soley responsible for insulin secretion in mammals, and which plays a prominent role in the control of circulating glucose and metabolism. Normal function of these islets implies the coordination of different types of endocrine cells, noticeably of the beta cells which produce insulin. Given that an appropriate secretion of this hormone is vital to the organism, a number of mechanisms have been selected during evolution, which now converge to coordinate beta cell functions. Among these, several mechanisms depend on different families of integral membrane proteins, which ensure direct (cadherins, N-CAM, occludin, and claudins) and paracrine communications (pannexins) between beta cells, and between these cells and the other islet cell types. Also, other proteins (integrins) provide communication of the different islet cell types with the materials that form the islet basal laminae and extracellular matrix. Here, we review what is known about these proteins and their signaling in pancreatic β-cells, with particular emphasis on the signaling provided by Cx36, given that this is the integral membrane protein involved in cell-to-cell communication, which has so far been mostly investigated for effects on beta cell functions. 1. Introduction In vertebrates, pancreatic beta cells are the sole source of the insulin hormone [1]. The modulation of insulin secretion as a function of the changing metabolic demand and environmental conditions, specifically the levels of circulating glucose, cannot be quantitatively fulfilled by a single beta cell. Indeed, the total amount of insulin of one cell (~10？pg) will not allow for establishment and maintenance of the basal circulating levels of the hormone (~1.25？mg/L in humans). Assuming that all beta cells of the million islets which are thought to be dispersed in a human pancreas contribute to these levels, this implies that about 125 cells should simultaneously secrete in each islet. After a meal, this number should increase by about 5 to 6-fold to rapidly establish the postprandial levels of insulin, which are required to maintain normoglycemia, and be tightly regulated to ensure the peripheral oscillations of the circulating levels of the hormone, which prevent the target tissues to establish a resistance to the hormone [2–4]. Eventually, the mechanism(s) controlling these surge and oscillations should also be able to synchronously turn off the secreting cells, in order to avoid dangerous hypoglycemia, once insulin has launched its
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