The contribution of store operated Ca2+ entry to respiration in endothelial cells and to Ca2+ homeostasis and basal insulin secretion in beta cellsCa2+ is an important signaling molecule within and between cells. While it is known for many years that Ca2+ activates some mitochondrial dehydrogenases resulting in increased mitochondrial respiration and ATP production, the source of Ca2+ was not investigated so far. The stimulation of endothelial cells with e.g. an IP3 generating agonist like histamine, leads to the depletion of the endoplasmic reticulum, resulting in an increase in mitochondrial Ca2+, both in the presence and in the absence of extracellular Ca2+. But in the presence of extracellular Ca2+ store depletion is followed by the so-called store operated Ca2+ entry (SOCE). We could demonstrate that stimulation of endothelial cells (EC) could only elicit an increased mitochondrial activity in the presence, of extracellular Ca2+, thus when SOCE is activated, pointing to a crucial role of SOCE for mitochondrial respiration in EC. In a 2nd approach we investigated the role of the stromal interacting protein 1 (Stim1) and Orai1, two key-proteins responsible for SOCE in many cell types, in a pancreatic ?-cell line. We transiently induced the co-expression of Stim1 and Orai1, which resulted in a strong increase of Ca2+ influx upon activation of SOCE, by store depletion with carbachol, caffeine or BHQ, while depolarization triggered Ca2+ influx through voltage gated L-type Ca2+ channels was unmodified. Downregulation of Stim1 supported these data. Co-expression of Stim1 and Orai1 resulted in an elevated cytosolic Ca2+ level under basal conditions, whereas it led to a pronounced Ca2+ depletion from the ER in the absence of extracelluar Ca2+. These data point to basal Ca2+ cycling in ?-cells that depends on Stim1 and Orai1. Our data let us suppose that this Stim1/Orai1 dependent Ca2+ cycling results in elevated insulin release under basal conditions.