Stimulative effects of TMB-8 and trifluoperazine on pancreatic hormone release

The effects of 8-N-N-diethylamino octyl 3,4,5-trimethoxybenzoate (TMB-8) and trifluoperazine (TFP) on the early phase (10 min) of the release of pancreatic hormones from isolated rat islets were investigated. TMB-8 and TFP stimulated insulin, glucagon, and somatostatin release in a dose-dependent manner at a low glucose concentration (2.5 mM). The levels of glucagon and somatostatin release were also stimulated by these two agents at a high glucose concentration (10 mM). Their effects were independent of external calcium ion level. These two agents did not modify insulin release at the high glucose concentration. The stimulative effects of the two agents on the release of these hormones were partially suppressed when the islets were pretreated with 6-hydroxydopamine (6-OHDA), a chemical adrenergic denervator that acts at nerve endings. In this situation, the norepinephrine (NE) released from pancreatic islets decreased to 44% of that of non-treated islets (P less than 0.01). The addition of NE (10(-9) M) to the incubation medium increased insulin, glucagon, and somatostatin secretion by 20-30% over control levels (P less than 0.05). In conclusion, the early phase of pancreatic hormone release was stimulated by TMB-8 and TFP. Our results strongly suggest that these two drugs could be mediated by the NE released from nerve endings in the islets.