The antidiabetic beta 3-adrenoceptor agonist BRL 26830A works by release of endogenous insulin.

A beta 3-adrenoceptor agonist, BRL 26830A, has been shown to have antiobesity and antidiabetic actions. However, the insulin-release mechanism of this agent is not well understood. Therefore, we tested the hypothesis that BRL 26830A promotes insulin release via beta 3 receptors on pancreatic-islet beta cells by using both in vivo and in vitro studies. In ICR mice fasted for 48 h, BRL 26830A significantly stimulated insulin release and markedly decreased the glucose level. Administration of a non-selective beta-receptor antagonist 30 min before BRL 26830A injection completely inhibited insulin release and the reduction of the glucose level. Neither beta 1- nor beta 2-selective antagonists produced the same effect. In the in vitro study with rat pancreatic-islet cell culture, BRL 26830A and its free acid BRL 28410 did not promote insulin secretion. The results of the in vivo studies support our hypothesis, but the results of the in vitro study showed some discrepancies.