The histaminergic mechanism of neurotensin-induced glucagon release from isolated rat pancreatic islets.

Isolated rat pancreatic islets were preincubated in a medium with 16.7 mM glucose and incubated with 5.5 mM glucose. Both histamine (100 microM) and neurotensin (100 nM) stimulated glucagon release from the isolated islets, but not insulin release. The stimulation of glucagon release occurred in the presence of 10 and 100 nM neurotensin, while the release of insulin was inhibited in the presence of 1 and 10 nM neurotensin. The neurotensin-induced glucagon release was completely inhibited by 1 mM metiamide, an histamine H2-receptor antagonist, added to the incubation medium and not inhibited by 1 mM diphenhydramine, an histamine H1-receptor antagonist. The results indicate that the histaminergic mechanism, including the H2-receptor system, may be involved in neurotensin-induced glucagon release from the endocrine pancreas.