The stimulus-secretion coupling of glucose-induced insulin release. XLV. The anion-osmotic hypothesis for exocytosis.
Replacement of extracellular chloride by the impermeant anion isethionate, increase in extracellular osmotic strength by addition of sucrose, or exposure to the anion transport blocking agent probenecid inhibited insulin release evoked by glucose or alpha-ketoisocaproate in rat isolated islets. The inhibition of insulin release due to Cl- substitution was associated with a modest decrease in glucose oxidation, but no significant change in glucose-stimulated 45Ca net uptake by the islets. In the isolated perfused rat pancreas, the isethionate- or sucrose-induced inhibition of insulin release was a rapid and rapidly reversible phenomenon. Chloride substitution by isethionate inhibited more severely the second than the first phase of the secretory response to glucose, and failed to affect the insulin response to gliclazide. A chemosmotic mechanism for exocytosis, as proposed for epinephrine and parathyroid hormone release, may also be involved in insulin release.
D000476:Alkanesulfonates / Q000494:pharmacology*; D000818:Animals; D005907:Gliclazide / Q000494:pharmacology; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007513:Isethionic Acid / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000378:metabolism*; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D013997:Time Factors
D000476:Alkanesulfonates; D007328:Insulin; D007513:Isethionic Acid; D005907:Gliclazide; D005947:Glucose; D011339:Probenecid