Effect of CL 316,243, a novel beta 3-adrenoceptor agonist, on insulin secretion in perfused mouse pancreas

In order to clarify the insulin-release mechanism of beta 3-adrenoceptor agonist, we examined the effect of CL 316,243, a highly specific beta 3-adrenoceptor agonist having a relative potency of beta 1:beta 2:beta 3 = 0:1:100,000, on insulin secretion in perfused mouse pancreas. The application of 0.2 mM and 0.5 mM CL 316,243 produced significant insulin secretion from within 1 min, which lasted until 2 min after its withdrawal. DL-propranolol and ICI 118551 at 0.2 mM partially inhibited the insulin secretion induced by the 0.2 mM CL 316,243, but 0.2 mM metoprolol had no effect on the insulin release produced by 0.2 mM CL 316,243. We conclude that beta 3-adrenoceptor agonist stimulates insulin secretion via beta 3-action in the perfused mouse pancreas.