PT  - JOURNAL ARTICLE
AU  - I-Min Liu
AU  - Wang-Chuan Chen
AU  - Juei-Tang Cheng
TI  - Mediation of β-Endorphin by Isoferulic Acid to Lower Plasma Glucose in Streptozotocin-Induced Diabetic Rats
AID  - 10.1124/jpet.103.053900
DP  - 2003 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1196--1204
VI  - 307
IP  - 3
4099  - http://jpet.aspetjournals.org/content/307/3/1196.short
4100  - http://jpet.aspetjournals.org/content/307/3/1196.full
SO  - J Pharmacol Exp Ther2003 Dec 01; 307
AB  - We investigated the mechanism(s) by which isoferulic acid lowers plasma glucose levels in streptozotocin-induced diabetic rats (STZ-diabetic rats). In STZ-diabetic rats, isoferulic acid dose dependently lowered plasma glucose concentrations and increased plasma β-endorphin-like immunoreactivity (BER). Both of these effects of isoferulic acid were abolished by pretreatment of rats with tamsulosin or 2-[2,6-dimethoxyphenoxyethyl]aminomethyl-1,4-benzodioxane hydrochloride (WB 4101) at doses sufficient to block α1-adrenoceptors. Also, isoferulic acid enhanced BER release from isolated rat adrenal medulla in a concentration-dependent manner that could be abolished by treatment with α1-adrenoceptor antagonists. Moreover, bilateral adrenalectomy in STZ-diabetic rats eliminated the activities of isoferulic acid, including the plasma glucose-lowering effect and the plasma BER-elevating effect. Naloxone and naloxonazine inhibited the plasma glucose-lowering activity of isoferulic acid at doses sufficient to block opioid μ-receptors. In contrast with the effect in wild-type diabetic mice, isoferulic acid failed to lower plasma glucose levels in opioid μ-receptor knockout diabetic mice. Treatment of STZ-diabetic rats with isoferulic acid three times in 1 day resulted in an increase in the expression of the glucose transporter subtype 4 form in soleus muscle. This effect was blocked by α1-adrenoceptor or opioid μ-receptor antagonists. The reduction of elevated mRNA or protein level of hepatic phosphoenolpyruvate carboxykinase was also impeded in the same groups of STZ-diabetic rats. In conclusion, our results suggest that isoferulic acid may activate α1-adrenoceptors to enhance the secretion of β-endorphin, which can stimulate the opioid μ-receptors to increase glucose use or/and reduce hepatic gluconeogenesis, resulting in a decrease of plasma glucose in STZ-diabetic rats. The American Society for Pharmacology and Experimental Therapeutics