Su C-F, Chang Y-Y, Pai H-H, Liu I-M, Lo C-Y, Cheng J-T
Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan, ROC.
Horm Metab Res. 2004 Aug;36(8):571-7. doi: 10.1055/s-2004-825763.
In an attempt to probe the effect of beta-endorphin on insulin resistance, we used Wistar rats that were fed fructose-rich chow to induce insulin resistance. Insulin action on glucose disposal rate (GDR) was measured using the hyperinsulinemic euglycemic clamp technique, in which glucose (variable), insulin (40 mU/kg/min), and beta-endorphin (6 ng/kg/min) or vehicle were initiated simultaneously and continued for 120 min. A marked reduction in insulin-stimulated GDR was observed in fructose-fed rats compared to normal control rats. Infusion of beta-endorphin reversed the value of GDR, which was inhibited by naloxone and naloxonazine each at doses sufficient to block opioid mu-receptors. Opioid mu-receptors may therefore be activated by beta-endorphin to improve insulin resistance. Next, soleus muscle was isolated to investigate the effect of beta-endorphin on insulin signals. Insulin resistance in rats induced by excess fructose was associated with the impaired insulin receptor (IR), tyrosine autophosphorylation, and insulin receptor substrate (IRS)-1 protein content in addition to the significant decrease in IRS-1 tyrosine phosphorylation in soleus muscle. This impaired glucose transportation was also due to signaling defects that included an attenuated p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3-kinase) and Akt serine phosphorylation. However, IR protein levels were not markedly changed in rats with insulin resistance. beta-endorphin infusion reversed the fructose-induced decrement in the insulin-signaling cascade with increased GDR. Apart from IR protein levels, infusion of beta-endorphin reversed the decrease in protein expression for the IRS-1, p85 regulatory subunit of PI3-kinase, and Akt serine phosphorylation in soleus muscle in fructose-fed rats. The decrease in insulin-stimulated protein expression of glucose transporter subtype 4 (GLUT 4) in fructose-fed rats returned to near-normal levels after beta-endorphin infusion. Infusion of beta-endorphin may improve insulin resistance by modulating the insulin-signaling pathway to reverse insulin responsiveness.
为了探究β-内啡肽对胰岛素抵抗的影响，我们使用喂食富含果糖食物的Wistar大鼠来诱导胰岛素抵抗。采用高胰岛素正常血糖钳夹技术测量胰岛素对葡萄糖处置率（GDR）的作用，在该技术中，葡萄糖（变量）、胰岛素（40 mU/kg/分钟）和β-内啡肽（6 ng/kg/分钟）或溶剂同时开始输注，并持续120分钟。与正常对照大鼠相比，喂食果糖的大鼠胰岛素刺激的GDR显著降低。输注β-内啡肽可使GDR值恢复正常，而纳洛酮和纳洛嗪在足以阻断阿片μ受体的剂量下均可抑制该作用。因此，β-内啡肽可能通过激活阿片μ受体来改善胰岛素抵抗。接下来，分离比目鱼肌以研究β-内啡肽对胰岛素信号的影响。除了比目鱼肌中胰岛素受体底物-1（IRS-1）酪氨酸磷酸化显著降低外，过量果糖诱导的大鼠胰岛素抵抗还与胰岛素受体（IR）受损、酪氨酸自身磷酸化以及IRS-1蛋白含量降低有关。这种葡萄糖转运受损还归因于信号缺陷，包括磷脂酰肌醇3激酶（PI3激酶）的p85调节亚基和Akt丝氨酸磷酸化减弱。然而，胰岛素抵抗大鼠的IR蛋白水平没有明显变化。输注β-内啡肽可逆转果糖诱导的胰岛素信号级联反应的降低，并提高GDR。除了IR蛋白水平外，输注β-内啡肽还可逆转喂食果糖大鼠比目鱼肌中IRS-1、PI3激酶p85调节亚基的蛋白表达降低以及Akt丝氨酸磷酸化。β-内啡肽输注后，喂食果糖大鼠胰岛素刺激的葡萄糖转运蛋白4（GLUT 4）亚型蛋白表达降低恢复到接近正常水平。输注β-内啡肽可能通过调节胰岛素信号通路来逆转胰岛素反应性，从而改善胰岛素抵抗。
