Granule fusion and fission (discharge) are biochemically dissociable events of exocytotic hormone release.
Granule fusion and the subsequent fission leading to hormone discharge are distinct and separable events in exocytosis. As an index of fusion, we followed the recruitment of granule-bound somatostatin receptors to the islet surface, an event which accompanies secretion vesicle migration and insulin secretion. Granule fission was monitored by measuring insulin release. Substitution of the impermeant salt sodium isethionate for NaCl led to a 90% decrease in glucose-stimulated insulin release with no inhibition of somatostatin receptor recruitment. The phenothiazine drugs, trifluoperazine and promethazine, believed to inhibit calcium-sensitive proteins involved with stimulus-secretion coupling blocked insulin release and somatostatin receptor recruitment in parallel. This suggests that these agents suppress intracellular events promoting fusion of the secretion granule with the plasma membrane. IBMX appears to stimulate specifically granule fission since IBMX-induced insulin release occurs acutely without an increase in somatostatin receptor recruitment. Sodium isethionate, which inhibits granule lysis, blocked IBMX-stimulated insulin release.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003411:Arvicolinae; D005089:Exocytosis / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007329:Insulin Antagonists / Q000494:pharmacology; D000078790:Insulin Secretion; D007513:Isethionic Acid / Q000494:pharmacology; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D011398:Promethazine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000378:metabolism*; D014268:Trifluoperazine / Q000494:pharmacology
D007328:Insulin; D007329:Insulin Antagonists; D014268:Trifluoperazine; D013004:Somatostatin; D007513:Isethionic Acid; D011398:Promethazine; D005947:Glucose; D015056:1-Methyl-3-isobutylxanthine