Mediation of beta-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 beta-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 mu-receptor antagonists and in opioid mu-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 mu-receptor blockade. Findings support the conclusion that the plasma glucose-lowering action of myricetin in insulin-deficient animals is mediated by activation of opioid mu-receptors of peripheral tissues in response to increased beta-endorphin secretion. Opioid mu-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.
Liu
I-Min
IM
Department of Pharmacy, Tajen University, Yanpu Shiang, Ping Tung Shien, Taiwan, ROC. iml@ccsun.tajen.edu.tw
Liou
Shorong-Shii
SS
Cheng
Juei-Tang
JT
D028483:Abelmoschus; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000096:biosynthesis / Q000172:deficiency; D001615:beta-Endorphin / Q000097:blood*
D001786:Blood Glucose; D005419:Flavonoids; D010936:Plant Extracts; D017450:Receptors, Opioid, mu; D001615:beta-Endorphin; C040015:myricetin