Olive Leaf Polyphenols (OLPs) Stimulate GLUT4 Expression and Translocation in the Skeletal Muscle of Diabetic Rats

Int J Mol Sci. 2020 Nov 26;21(23):8981. doi: 10.3390/ijms21238981.

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.

Keywords: GLUT4 translocation; Rab13; Rab14; Rab8A; diabetes mellitus; glucose transporter 4; skeletal muscle.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / metabolism*
  • Glucose Tolerance Test
  • Glucose Transporter Type 4 / metabolism*
  • Male
  • Membranes
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Olea / chemistry*
  • Plant Leaves / chemistry*
  • Polyphenols / pharmacology*
  • Protein Transport / drug effects
  • Rats, Wistar
  • rab GTP-Binding Proteins / metabolism

Substances

  • Glucose Transporter Type 4
  • Polyphenols
  • rab GTP-Binding Proteins