Effects of a β₃-Adrenoceptor Agonist, BRL 26830A, on Insulin and Glucagon Release in Mice

Abstract

The β₃-adrenoceptor agonist, BRL 26830A, which is not inhibited by either β₁ or β₂-selective antagonists, has been shown to possess anti-obesity and anti-diabetic actions. However, the effects of this agent on insulin and glucagon release have not yet been substantiated. Therefore, we tested the hypothesis that BRL 26830A promotes insulin and glucagon secretion via β₃ receptors on pancreatic islet B and A cells. In ICR mice fasted for 48 h, BRL 26830A significantly stimulated insulin secretion from 5 min after administration, markedly decreased blood glucose levels from 30 min after administration, and significantly increased glucagon secretion from 30 min after administration. The administration of a non-selective β-receptor antagonist, at a dose of 50mg/kg, 30 min prior to BRL 26830A injection completely abolished the effects induced by BRL 26830A. However, the administration of a β₁-selective antagonist at doses of 50 or 100 mg/kg did not produce any significant effects. On the action of BRL 26830A, whereas the administration of a β₂-selective antagonist at 50mg/kg, a near maximal effective dose, partially abolished the effects of BRL 26830A. BRL 26830A had no effect on insulin, glucagon, or glucose levels in streptozocin (STZ) diabetic mice fasted for 48 h. These results suggest that, in mice, BRL 26830A may promote insulin secretion mainly via β₃ receptors and partially via β₂ receptors on pancreatic-islet B cells, and that glucagon may be secreted as the result of hypoglycemia induced by this agent.