Glucose dose-related influence of phospholipase C and melittin on insulin release from perifused rat islets

We studied the influence of exogenous phospholipase C (20 mU/ml) and melittin (25 micrograms/ml) on glucose-induced insulin release to further assess the role of Pl turnover as an important component in signal transduction in the B-cells. The secretory response to both substances was rapid and biphasic. However, phospholipase C did not, like melittin, elicit a secretory response in the absence of glucose. Phospholipase C elicited a half-maximal response at 4.5 mM and melittin at 2.0 mM glucose. Phospholipase C also enhanced the maximum amount of insulin release. Mannoheptulose markedly inhibited the secretory response of both melittin and phospholipase C in the presence of glucose, but the secretory effect of melittin, in the absence of glucose was not influenced. The results indicate that both melittin and phospholipase C elicit a secretory effect dependent on intact glucose metabolism. However, the variability of the effects of each agent on the glucose-dose related secretory response indicates that melittin may influence insulin release in a manner independent of nutrient metabolism and phospholipase C activity.