Department of Biotechnology, University of Rijeka, Radmile Matejčić 2, 51000 Rijeka, Croatia.
Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia.
Int J Mol Sci. 2020 Nov 26;21(23):8981. doi: 10.3390/ijms21238981.
Skeletal muscles are high-insulin tissues responsible for disposing of glucose via the highly regulated process of facilitated glucose transporter 4 (GLUT4). Impaired insulin action in diabetes, as well as disorders of GLUT4 vesicle trafficking in the muscle, are involved in defects in insulin-stimulated GLUT4 translocation. Since the Rab GTPases are the main regulators of vesicular membrane transport in exo- and endo-cytosis, in the present work, we studied the effect of olive leaf polyphenols (OLPs) on Rab8A, Rab13, and Rab14 proteins of the rat soleus muscle in a model of streptozotocin (SZT)-induced diabetes (DM) in a dose-dependent manner. Glucose, cholesterol, and triglyceride levels were determined in the blood, morphological changes of the muscle tissue were captured by hematoxylin and eosin histological staining, and expression of GLUT4, Rab8A, Rab13, and Rab14 proteins were analyzed in the rat soleus muscle by the immunofluorescence staining and immunoblotting. OLPs significantly reduced blood glucose level in all treated groups. Furthermore, significantly reduced blood triglycerides were found in the groups with the lowest and highest OLPs treatment. The dynamics of activation of Rab8A, Rab13, and Rab14 was OLPs dose-dependent and more effective at higher OLP doses. Thus, these results indicate a beneficial role of phenolic compounds from the olive leaf in the regulation of glucose homeostasis in the skeletal muscle.
骨骼肌是高胰岛素组织,通过高度调节的易化葡萄糖转运蛋白 4(GLUT4)过程来处理葡萄糖。糖尿病中胰岛素作用受损以及肌肉中 GLUT4 囊泡运输紊乱,都涉及胰岛素刺激的 GLUT4 易位缺陷。由于 Rab GTPases 是外泌体和内体中囊泡膜运输的主要调节剂,在本工作中,我们研究了橄榄叶多酚(OLPs)对链脲佐菌素(SZT)诱导的糖尿病(DM)大鼠比目鱼肌中 Rab8A、Rab13 和 Rab14 蛋白的影响,剂量依赖性方式。在血液中测定了葡萄糖、胆固醇和甘油三酯水平,通过苏木精和曙红组织学染色观察肌肉组织的形态变化,通过免疫荧光染色和免疫印迹分析大鼠比目鱼肌中 GLUT4、Rab8A、Rab13 和 Rab14 蛋白的表达。OLPs 显著降低了所有治疗组的血糖水平。此外,在 OLP 处理的最低和最高组中,发现血甘油三酯显著降低。Rab8A、Rab13 和 Rab14 的激活动力学与 OLP 剂量呈剂量依赖性,在较高的 OLP 剂量下更有效。因此,这些结果表明,来自橄榄叶的酚类化合物在调节骨骼肌葡萄糖稳态方面发挥有益作用。