Mediation of β-endorphin by myricetin to lower plasma glucose in streptozotocin-induced diabetic rats

Streptozotocin-induced diabetic (STZ-diabetic) rats were employed to investigate the mechanism(s) whereby myricetin, the active principle of Abelmoschus moschatus (Malvaceae), exerts its glucose-lowering effects. Myricetin was purified from the aerial portion of the plant and administered intravenously. A dose-dependent decrease in plasma glucose concentration was observed 30 min following injection, in parallel with increased plasma β-endorphin-like immunoreactivity (BER). Myricetin enhanced BER release similarly from isolated adrenal medulla. Plasma glucose-lowering and BER-elevating effects of myricetin were both eliminated after bilateral adrenalectomy. Myricetin failed to lower plasma glucose after treatment with opioid μ-receptor antagonists and in opioid μ-receptor knockout diabetic mice. Injection of myricetin three times daily for three consecutive days resulted in increased expression of the glucose transporter subtype 4 (GLUT 4) in soleus muscle and in reduced expression of phosphoenolpyruvate carboxykinase (PEPCK) in liver; these inductions were preventable by opioid μ-receptor blockade. Findings support the conclusion that the plasma glucose-lowering action of myricetin in insulin-deficient animals is mediated by activation of opioid μ-receptors of peripheral tissues in response to increased β-endorphin secretion. Opioid μ-receptor activation is held responsible for the enhancement of muscle GLUT 4 gene expression and the attenuation of hepatic PEPCK gene expression observed in these myricetin-treated diabetic animals.