Cerebellin potently stimulates norepinephrine release by rat adrenal medulla, acting through adenylate-cyclase/PKA-coupled receptors, and enhances adrenocortical steroid secretion in vivo (i.e. when the integrity of adrenal gland is preserved) through an indirect paracrine mechanism involving the release of medullary catecholamines. Cerebellin reduces plasma insulin levels in rats after 1 and 2 h. Cerebellin decreases insulin secretion from isolated rat pancreatic islets at high (11 mM), but not at low (3.33 mM) glucose concentration. Cerebellin inhibits stimulated insulin secretion from clonal rat insulinoma (INS-1) cells, reduces forskolin-induced production of cAMP and intracellular calcium concentration.