Secretion of insulin could be stimulated by several ways. Comparison of glucose- and swelling induced mechanisms in pancreatic islets revealed the involvement of a novel signal transduction pathway with specific features of osmotically stimulated peptide hormone release including Ca²⁺ independence and resistance to noradrenalin inhibition. Cell swelling can be induced by hypotonicity or small permeant molecules (e.g. ethanol, urea). Objective of this study was characterization of ethanol-induced insulin secretion. Signaling of ethanol- and glucose-induced insulin release from INS-1 and INS-1E cells was compared. Both cell lines responded similarly to all experimental interventions. In contrast to glucose, ethanol-induced insulin secretion was not hindered in calcium depleted medium or by addition of 10 mmol/l BAPTA/AM (intracellular chelator). Inhibitor of protein kinase C Bisindolylmaleimide (3 mmol/l) in contrast to glucose stimulation did not inhibit ethanol-induced insulin secretion. Tetanus toxin (20 nmol/l), inhibitor of SNARE proteins complex formation, blocked ethanol-induced insulin secretion. 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 ethanol stimulation in either treatment.

Conclusion: 

Signaling of ethanol-induced insulin secretion from INS-1 and INS-1E cell lines bypasses calcium and PKC involving steps, is sensitive to tetanus toxin but resistant to N-ethymaleimide and ZnCl₂. An extra pool of secretory vesicles not available for glucose is exploited for exocytosis after ethanol stimulation.

Supported by APVV 0235-06, APVV VVCE-0064-07, APVV RPEU 0007-06, CENDO SAV, VEGA 2/0094/09.