Gallic acid attenuates high-fat diet fed-streptozotocin-induced insulin resistance via partial agonism of PPAR gamma in experimental type 2 diabetic rats and enhances glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway

摘要

In this study, the therapeutic efficacy of gallic acid from Cyarnopsis tetragonoloba (L) Taub. (Fabaceae) beans was examined against high-fat diet fed-streptozotocin-induced experimental type 2 diabetic rats. Molecular-dockings were done to determine the putative binding modes of gallic acid into the active sites of key insulin-signaling markers. Gallic acid (20 mg/kg) given to high-fat diet fed-streptozotocininduced rats lowered body weight gain, fasting blood glucose and plasma insulin in diabetic rats. It further restored the alterations of biochemical parameters to near normal levels in diabetic treated rats along with cytoprotective action on pancreatic beta-cell. Histology of liver and adipose tissues supported the biochemical findings. Gallic acid significantly enhanced the level of peroxisome proliferator-activated receptor gamma (PPAR gamma) expression in the adipose tissue of treated rat compared to untreated diabetic rat; it also slightly activated PPAR gamma expressions in the liver and skeletal muscle. Consequently, it improved insulin dependent glucose transport in adipose tissue through translocation and activation of glucose transporter protein 4 (GLUT4) in phosphatidylinositol 3-kinase (PI3K)/phosphorylated protein kinase B (p-Akt) dependent pathway. Gallic acid docked with PPAR gamma; it exhibited promising interactions with the GLUT4, glucose transporter protein 1 (GLUT1), PI3K and p-Akt. These findings provided evidence to show that gallic acid could improve adipose tissue insulin sensitivity, modulate adipogenesis, increase adipose glucose uptake and protect beta-cells from impairment. Hence it can be used in the management of obesityassociated type 2 diabetes mellitus. (C) 2014 Elsevier B.V. All rights reserved.