Is there a role for osmotic events in the exocytotic release of insulin?
The possible role of an osmotic lysis of insulin granules during exocytosis has been studied in perifused mouse pancreatic islets. Raising the osmolarity of the extracellular medium by addition of 400 mM sucrose reversibly inhibited glucose-stimulated insulin release. This inhibition was accompanied by a decrease in the rates of 86Rb+ or 45Ca2+ efflux from the islets. Increasing the osmolarity and restoring a normotonic medium in the presence of a nonstimulatory concentration of glucose accelerated 86Rb+ and 45Ca2+ efflux and augmented basal insulin release in both the presence and absence of Ca2+. Hyperosmolarity did not prevent a rise in glucose concentration from decreasing 86Rb+ efflux from islet cells or from inhibiting 45Ca2+ efflux in Ca2+-free medium. However, the stimulation of 45Ca2+ efflux otherwise produced by glucose in the presence of Ca2+ was abolished, and the stimulation of insulin release was almost suppressed. Hyperosmolarity also strongly impaired the release of insulin during stimulation by eight experimental conditions known to act through at least partially different mechanisms. The changes in 45Ca2+ efflux brought about by these different agents were also altered by hyperosmolarity, whether they resulted from direct mobilization of intracellular Ca2+ or were secondary to increased Ca2+ influx. The blockade of insulin release by hyperosmolarity, whatever the mode of action of the stimulus, is compatible with the participation of osmotic events in exocytosis. However, the marked alterations in Ca2+ handling that occur concomitantly and might account for the inhibition of release make it impossible to demonstrate their exact role in intact islet cells.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003470:Culture Media / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000378:metabolism; D005089:Exocytosis; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006982:Hypertonic Solutions / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D009995:Osmosis; D012413:Rubidium / Q000378:metabolism; D012636:Secretory Rate / Q000187:drug effects
D003470:Culture Media; D006982:Hypertonic Solutions; D007328:Insulin; D005947:Glucose; D012413:Rubidium; D002118:Calcium