Control of secretion vesicle margination and lysis by glucose, IBMX, and glyburide

We have attempted to define the effect of glucose, glyburide, and isobutylmethylxanthine (IBMX) upon secretion vesicle margination to the plasma membrane and granule lysis. Margination of secretion vesicles during exocytosis was assessed by measuring the recruitment of somatostatin (SRIF) receptors. Secretion vesicle lysis was studied by measuring insulin release into the incubation media. Our observations suggest that glucose directly affects both secretion vesicle margination and lysis. Both events are rapidly influenced by this secretagogue (within 10 min of incubation). Trifluoperazine (TFP) and removal of Ca2+ from the incubation media significantly reduced glucose-induced margination of secretion vesicles and their lysis (P less than 0.001). IBMX primarily influences the lysis of secretion vesicles and not their margination. IBMX caused a rapid increase in insulin secretion within 10 min without recruitment of SRIF receptors. Neither TFP nor the absence of extracellular Ca2+ affected IBMX-induced insulin release. Late enhancement in margination of secretion vesicles (30 min of incubation with IBMX) is probably related to the initial event of secretion vesicle lysis and is independent of extracellular calcium. Glyburide exerts its action in a manner similar to glucose, affecting both the lysis of secretion vesicles and their margination. However, the action of glyburide is independent of extracellular calcium and partially dependent upon calmodulin.