Title：Mediation of beta-endorphin by isoferulic acid to lower plasma glucose in streptozotocin-induced diabetic rats

标题：异阿魏酸通过β-内啡肽介导降低链脲佐菌素诱导的糖尿病大鼠血糖的作用

Authors: I-Min Liu, Wang-Chuan Chen, Juei-Tang Cheng

作者：刘怡民、陈旺川、郑瑞棠

Journal Information: Journal of Pharmacology and Experimental Therapeutics, December 2003, Volume 307, Issue 3, Pages 1196-1204

期刊信息：药理学与实验治疗学杂志，2003年12月，307卷，第3期，1196-1204页

Abstract

The study investigates how isoferulic acid (IFA) lowers plasma glucose levels in streptozotocin (STZ)-induced diabetic rats. The research shows that IFA dose-dependently lowers plasma glucose levels and increases plasma beta-endorphin-like immunoreactivity (BER). These effects are blocked by alpha1-adrenoceptor antagonists, suggesting that IFA enhances BER release through alpha1-adrenoceptor activation. Additionally, the glucose-lowering and BER-elevating effects of IFA are eliminated by bilateral adrenalectomy and blocked by opioid mu-receptor antagonists. IFA also increases the expression of the glucose transporter subtype 4 (GLUT4) in soleus muscle, and reduces hepatic phosphoenolpyruvate carboxykinase (PEPCK) mRNA and protein levels. The study concludes that IFA may lower plasma glucose by enhancing beta-endorphin secretion and stimulating opioid mu-receptors.

摘要

本研究探讨了异阿魏酸（IFA）如何降低链脲佐菌素（STZ）诱导的糖尿病大鼠的血浆葡萄糖水平。研究表明，IFA剂量依赖性地降低血浆葡萄糖水平并增加血浆β-内啡肽样免疫反应（BER）。这些效应被α1-肾上腺素受体拮抗剂阻断，表明IFA通过激活α1-肾上腺素受体增强BER释放。此外，IFA的降糖和BER增加效应被双侧肾上腺切除术消除，并被阿片μ受体拮抗剂阻断。IFA还增加肌肉中的葡萄糖转运蛋白亚型4（GLUT4）的表达，并减少肝脏磷酸烯醇式丙酮酸羧激酶（PEPCK）的mRNA和蛋白质水平。研究得出结论，IFA可能通过增强β-内啡肽分泌和刺激阿片μ受体来降低血浆葡萄糖。

Key Findings

1.IFA and Plasma Glucose Levels:

IFA lowers plasma glucose levels in STZ-diabetic rats.

The effect is dose-dependent.

2.Beta-Endorphin Release:

IFA increases plasma beta-endorphin-like immunoreactivity (BER).

The effect is mediated through alpha1-adrenoceptors.

BER release from the adrenal medulla is concentration-dependent and blocked by alpha1-adrenoceptor antagonists.

3.Adrenal Glands and Glucose Lowering:

Bilateral adrenalectomy abolishes IFA's glucose-lowering and BER-elevating effects.

4.Opioid Receptor Involvement:

Naloxone and naloxonazine, opioid mu-receptor antagonists, inhibit IFA's glucose-lowering activity.

IFA does not lower plasma glucose in opioid mu-receptor knockout mice.

5.Glucose Transporter and Gluconeogenesis:

IFA increases GLUT4 expression in muscle.

Reduces hepatic PEPCK mRNA and protein levels.

Both effects are blocked by alpha1-adrenoceptor or opioid mu-receptor antagonists.

主要发现

1.IFA与血浆葡萄糖水平：

IFA降低STZ糖尿病大鼠的血浆葡萄糖水平。

效果具有剂量依赖性。

2.β-内啡肽释放：

IFA增加血浆β-内啡肽样免疫反应（BER）。

效应通过α1-肾上腺素受体介导。

肾上腺髓质中BER的释放与浓度依赖性相关，并被α1-肾上腺素受体拮抗剂阻断。

3.肾上腺与降糖作用：

双侧肾上腺切除术消除IFA的降糖和BER增加效应。

4.阿片受体的参与：

纳洛酮和纳洛芬（阿片μ受体拮抗剂）抑制IFA的降糖活性。

IFA不能降低阿片μ受体敲除小鼠的血浆葡萄糖水平。

5.葡萄糖转运蛋白与糖异生：

IFA增加肌肉中GLUT4的表达。

减少肝脏PEPCK的mRNA和蛋白质水平。

这些效应均被α1-肾上腺素受体或阿片μ受体拮抗剂阻断。

Relevant Compounds and CAS Numbers

1. Isoferulic Acid (IFA) - CAS: 537-73-5
2. Streptozotocin (STZ) - CAS: 18883-66-4
3. Tamsulosin - CAS: 106133-20-4

相关化合物及CAS号

1. 异阿魏酸（Isoferulic Acid, IFA） - CAS号: 537-73-5
2. 链脲佐菌素（Streptozotocin, STZ） - CAS号: 18883-66-4
3. 坦索罗辛（Tamsulosin） - CAS号: 106133-20-4