In vitro insulinotropic action of a new non-sulfonylurea hypoglycemic agent, calcium (2s)-2-benzyl-3-(cis-hexahydro-2-isoindolinyl-carbonyl) propionate dihydrate (KAD-1229), in rat pancreatic B-cells.
Noradrenaline (1-10 microM) inhibited Ca2+-induced insulin secretion from electrically permeabilised islets of Langerhans with an efficacy similar to that for inhibition of glucose-induced insulin secretion from intact islets. The inhibition of insulin secretion from permeabilised islets was blocked by the alpha 2-adrenoreceptor antagonist, yohimbine. Adenosine 3',5'-cyclic monophosphate (cAMP) did not relieve the noradrenaline inhibition of Ca2+-induced secretion from the permeabilised islets, although noradrenaline did not affect the secretory responses to cAMP at substimulatory (50 nM) concentrations of Ca2+. These results suggest that catecholamines do not inhibit insulin secretion solely by reducing B-cell adenylate cyclase activity, and imply that one site of action of noradrenaline is at a late stage in the secretory process.