Swelling-induced peptide secretion represents cellular reaction when material stored in secretory vesicles is expulsed from various types of cells. The exocytosis induced by cell swelling is a broad unspecific phenomenon affecting many hormones, enzymes and bioactive peptides after exposure of cells to relative hyposmolarity or treatment with permeant agents. Dynamics of secretion is indistinguishable from that induced by specific secretagogue. Cell swelling represents alternative way of stimulation of secretion since its signaling pathway bypasses Ca²⁺ involving steps and conventional intracellular signal mediators and is resistant to physiological inhibitors. Both 5 mmol/l N-ethylamaleimide and 10 mmol/l ZnCl₂ (inhibitor of protein tyrosine phosphatases), which block disassembly of SNARE complexes and their further participation in exocytosis, increased basal insulin secretion. In contrast to glucose, already high insulin secretion was further increased after cell swelling. In contrast to conventional stimulation an extra pool of secretory granules is available for swelling-induced insulin exocytosis. Cell swelling could be important mediator of changes, which take place at pathophysiological conditions; shift to anaerobic glycolysis and production of metabolites in ischemia increase intracellular osmolarity, thus increasing transmembrane osmotic pressure differences and producing cell swelling. Products released after swelling could participate in the development of ischemia-reperfusion injury, but could be also mediators of local or remote preconditioning when factors released at the place of ischemia have protective effect. Perfusion of isolated rat heart with hyperosmolar high glucose medium followed by washout with isosmolar medium (relative hyposmotic stress) prior to ischemia substantially decreased postischemic contractile dysfunction, size of myocardial infarction and the severity of reperfusion-induced arrhythmias. Sustained perfusion with hyperosmolar high glucose medium without washout period with isosmolar medium did not have any protective effect on ischemia-reperfusion injury thus indicating important role of cell swelling. PI3K/Akt inhibitor wortmannin (100 nM) completely abolished improved contractile function recovery and increased the size of infarction, but failed to reverse lower severity of arrhythmias. In conclusion: Factors released during relative hyposmotic stress (washout period) most likely participate in the mechanism of preconditioning.

Supported by projects: VEGA 2/0094/09, APVV 0235-06, 2/0173/08, APVV VVCE-0064-07, CENDO and CEKVY SAS.