Effects of imidazoline derivative RX871024 on insulin, glucagon, and somatostatin secretion from isolated perfused rat pancreas

The effects of the imidazoline compound RX871024 on arginine-induced insulin, glucagon, and somatostatin secretion in the isolated perfused rat pancreas have been investigated. Arginine induced biphasic insulin, glucagon, and somatostatin release when infused for 20 min at 20 mM concentration and 3.3 mM glucose in the medium. RX871024, at 10 μM, did not influence basal hormone secretion but enhanced arginine-stimulated insulin and somatostatin release. In contrast, glucagon secretion was markedly inhibited by 10 μM imidazoline. RX871024 (1 μM) did not significantly affect arginine-induced insulin and somatostatin secretion but had an inhibitory effect on the second phase of glucagon release. In conclusion, RX871024 exerts a complex effect on the endocrine pancreas challenged by arginine, comprising stimulation of insulin and somatostatin release and inhibition of glucagon release. These effects on hormone release probably constitute the main mechanism of the antidiabetogenic action of the imidazolines.