Pancreatic beta cells secrete insulin in response to elevated plasma glucose levels in a Ca2+‐dependent fashion. Released insulin may act on the beta cell itself to promote further insulin synthesis and release. Recent studies by Johnson and Misler,1 Masgrau et al.2 and Mitchell et al.3 provide strong evidence (1) for the existence of intracellular Ca2+ stores sensitive to NAADP, a potent Ca2+‐mobilizing messenger, and (2) that these Ca2+ stores are involved in both glucose‐ and insulin‐mediated signal transduction. NAADP (...) may therefore play an important role in controling secretion of insulin from pancreatic beta cells. BioEssays 25:430–433, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

SummaryMuch excitement surrounded the proposal that a family of endo‐lysosomal channels, the two‐pore channels (TPCs) were the long sought after targets of the Ca2+‐mobilising messenger, nicotinic acid adenine dinucleotide phosphate (NAADP). However, the role of TPCs in NAADP signalling may be more complex than originally envisaged. First, NAADP may not bind directly to TPCs but via an accessory protein. Second, two papers recently challenged the notion that TPCs are NAADP‐regulated Ca2+ channels by suggesting that they are (...) highly selective Na+ channels regulated by the lipid phosphatidylinositol 3,5‐bisphosphate and by ATP. This paper aims critically to evaluate the evidence for TPCs as NAADP targets and to discuss how the new findings fit in with what we know about endo‐lysosomal Ca2+ stores. (shrink)