title: Gallic acid attenuates high-fat diet fed-streptozotocin-induced insulin resistance via partial agonism of PPARγ in experimental type 2 diabetic rats and enhances glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway.
abstract: In this study, the therapeutic efficacy of gallic acid from Cyamopsis 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-streptozotocin-induced 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 β-cell. Histology of liver and adipose tissues supported the biochemical findings. Gallic acid significantly enhanced the level of peroxisome proliferator-activated receptor γ (PPARγ) expression in the adipose tissue of treated rat compared to untreated diabetic rat; it also slightly activated PPARγ 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 PPARγ; 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 β-cells from impairment. Hence it can be used in the management of obesity-associated type 2 diabetes mellitus.
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai 600034, India.
authors.forename: Gopalsamy Rajiv
authors.initials: GR
authors.lastname: Gandhi
authors.affiliation: Department of Biochemistry, Srimad Andavan Arts and Science College, Tiruchirapalli 620005, India.
authors.forename: Gnanasekaran
authors.initials: G
authors.lastname: Jothi
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai 600034, India.
authors.forename: Poovathumkal James
authors.initials: PJ
authors.lastname: Antony
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai 600034, India.
authors.forename: Kedike
authors.initials: K
authors.lastname: Balakrishna
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai 600034, India.
authors.forename: Michael Gabriel
authors.initials: MG
authors.lastname: Paulraj
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai 600034, India. Electronic address: eriloyola@hotmail.com.
authors.forename: Savarimuthu
authors.initials: S
authors.lastname: Ignacimuthu
authors.affiliation: Division of Bioinformatics, Entomology Research Institute, Loyola College, Chennai 600034, India.
authors.forename: Antony
authors.initials: A
authors.lastname: Stalin
authors.affiliation: Department of Botany and Microbiology, Adirayah Chair for Environmental Studies, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Naif Abdullah
authors.initials: NA
authors.lastname: Al-Dhabi
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D005707:Gallic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D008958:Models, Molecular; D047495:PPAR gamma / Q000819:agonists* / Q000737:chemistry / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin / Q000633:toxicity
chemical_list: D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; C495694:Slc2a4 protein, rat; D013311:Streptozocin; D005707:Gallic Acid; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose
keywords: Cyamopsis tetragonoloba; GLUT4; Gallic acid; PI3K/p-Akt; PPARγ; Type 2 diabetes mellitus