title: Reversal of dexamethasone induced insulin resistance in 3T3L1 adipocytes by 3β-taraxerol of Mangifera indica.
abstract: OBJECTIVE
  The present study investigates the efficacy of Mangifera indica ethyl acetate extract (MIEE) and its bioactive compound, 3β-taraxerol in the reversal of dexamethasone (DEX) induced insulin resistance in 3T3L1 adipocytes.
  
  
  METHODS
  MIEE and 3β-taraxerol were evaluated for their ability to restore impaired glucose uptake and, expression of molecular markers in the insulin signaling pathway induced by DEX in 3T3L1 adipocytes using 2-deoxy-D-[1-(3)H] glucose uptake assay and ELISA.
  
  
  RESULTS
  An insulin resistant model has been developed using a glucocorticoid, DEX on 3T3L1 adipocytes. Insulin resistant condition was observed at 24h of DEX induction wherein a maximum degree of resistance of about 50% was measured based on inhibition of glucose uptake, which was confirmed using cytotoxicity analysis. The developed model of insulin resistance was studied in comparison to positive control rosiglitazone. DEX induced inhibition of glucose uptake and the expression of insulin signaling markers GLUT4 and PI3K were found to be restored by 3β-taraxerol and MIEE, thus delineating its mechanism of action in the reversal of insulin resistance.
  
  
  CONCLUSIONS
  3β-Taraxerol effectively restored DEX induced desensitization via restoration of PI3K and GLUT4 expression. To conclude, since 3β-taraxerol exhibits significant effect in reversing insulin resistance it can be further investigated as an insulin resistance reversal agent.
authors.affiliation: Centre for Biotechnology, Anna University, Chennai, India.
authors.forename: K N
authors.initials: KN
authors.lastname: Sangeetha
authors.forename: K
authors.initials: K
authors.lastname: Shilpa
authors.forename: P
authors.initials: P
authors.lastname: Jyothi Kumari
authors.forename: B S
authors.initials: BS
authors.lastname: Lakshmi
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003907:Dexamethasone / Q000633:toxicity; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006946:Hyperinsulinism / Q000139:chemically induced / Q000188:drug therapy; D007004:Hypoglycemic Agents; D007333:Insulin Resistance; D031022:Mangifera / Q000737:chemistry*; D051379:Mice; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D000077154:Rosiglitazone; D045162:Thiazolidinediones
chemical_list: D015415:Biomarkers; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; C501277:Mangifera indica extract; D010936:Plant Extracts; C495693:Slc2a4 protein, mouse; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D009828:Oleanolic Acid; D003907:Dexamethasone; C005802:taraxerol; D019869:Phosphatidylinositol 3-Kinases; D005947:Glucose