Abstract
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.
Highlights
Glucose metabolism is a good example of communication and signalling in the organism, and the investigation of its transport and delivery in specific tissues such as skeletal muscle is important for the maintenance of the whole-body glucose homeostasis [1]
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
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 glucose transporter 4 (GLUT4), Rab8A, Rab13, and Rab14 proteins were analyzed in the rat soleus muscle by the immunofluorescence staining and immunoblotting
Summary
Glucose metabolism is a good example of communication and signalling in the organism, and the investigation of its transport and delivery in specific tissues such as skeletal muscle is important for the maintenance of the whole-body glucose homeostasis [1]. The glucose transporter 4 (GLUT4) controls cellular glucose transport into skeletal muscles and adipose tissues in response to insulin stimulation [2]. Two pathways have been identified in the mechanism of GLUT4 translocation stimulated by insulin, (i) the protein kinases-activated pathways including phosphoinositide-3-kinase (PI3K) and the mitogen-activated protein kinase 3/1 (MAPK3/1, ERK1/2), and (ii) the Cb1-CAP-CrkII-C3G-TC10 pathway. The correct functioning of the PI3K/AKT, MAPK, and AMPK pathways is essential for proper metabolic control. Their dysfunction impairs glucose homeostasis [5,6]
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