title: Flavonoids from Enicostema littorale blume enhances glucose uptake of cells in insulin resistant human liver cancer (HepG2) cell line via IRS-1/PI3K/Akt pathway.
abstract: Diabetes mellitus has spread over the world with 347 million people affected. Insulin resistance is a main pathogenic event in Type 2 Diabetes Mellitus (T2DM) leading to a reduction in glucose uptake by peripheral tissue and increased hepatic glucose output. In this study, we have isolated four flavonoid rich fractions fraction A (FA), fraction B (FB), fraction C (FC) and fraction D (FD) from Enicostema littorale. All the fractions were preliminary screened for TLC fingerprinting, total flavonoid content. Total eight flavonoids were identified by LC/MS. Insulin resistant HepG2 (IR/HepG2) model was established by inducing insulin resistance in HepG2 cells to investigate the effect of these fractions on IR/HepG2 cell line for their glucose uptake. The results showed the significant dose dependant increase in glucose uptake of cells treated with FD. It showed significant activity at a concentration of 10μg/ml. The LC/MS results of FD demonstrated the presence of C-glycoside Swertisin which could be responsible for the effect. Further, to investigate the mechanism of action, gene expression for insulin receptor substrate 1 (IRS-1), protein kinase B (Akt-2) and glucose transporter 4 (GLUT-4) genes were evaluated by real time PCR. A significant upregulation of these genes was observed in FD treated samples, thereby indicating the enhancement of glucose uptake rate of cells via IRS-1/PI3K/Akt pathway.
authors.affiliation: Department of Biological Sciences, Sunandan Divatia School of Science, NMIMS University, Vile Parle (West), Mumbai, 400056, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Mokashi
authors.affiliation: Department of Biological Sciences, Sunandan Divatia School of Science, NMIMS University, Vile Parle (West), Mumbai, 400056, India.
authors.forename: Aparna
authors.initials: A
authors.lastname: Khanna
authors.affiliation: Department of Chemistry, Sunandan Divatia School of Science, NMIMS University, Vile Parle (West), Mumbai, 400056, India. Electronic address: nancy.pandita@nmims.edu.
authors.forename: Nancy
authors.initials: N
authors.lastname: Pandita
mesh_terms: D045744:Cell Line, Tumor; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D029965:Gentianaceae / Q000737:chemistry*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006027:Glycosides; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008113:Liver Neoplasms; D009005:Monosaccharides / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D005419:Flavonoids; D005947:Glucose; D051275:Glucose Transporter Type 4; D006027:Glycosides; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D009005:Monosaccharides; D019869:Phosphatidylinositol 3-Kinases; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin; C438934:C-glycoside; C526292:IRS1 protein, human
keywords: E. littorale; Flavonoids; Glucose transporters; Glucose uptake assay; HepG2 cell line; Insulin receptors; LC/MS