title: Insulin sensitization via partial agonism of PPARγ and glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway by embelin in type 2 diabetic rats.
abstract: BACKGROUND
  The present study was aimed at isolating an antidiabetic molecule from a herbal source and assessing its mechanism of action.
  
  
  METHODS
  Embelin, isolated from Embelia ribes Burm. (Myrsinaceae) fruit, was evaluated for its potential to regulate insulin resistance, alter β-cell dysfunction and modulate key markers involved in insulin sensitivity and glucose transport using high-fat diet (HFD) fed-streptozotocin (STZ) (40mg/kg)-induced type 2 diabetic rats. Molecular-dockings were performed to investigate the binding modes of embelin into PPARγ, PI3K, p-Akt and GLUT4 active sites.
  
  
  RESULTS
  Embelin (50mg/kg b wt.) reduced body weight gain, blood glucose and plasma insulin in treated diabetic rats. It further modulated the altered lipid profiles and antioxidant enzymes with cytoprotective action on β-cell. Embelin significantly increased the PPARγ expression in epididymal adipose tissue compared to diabetic control group; it also inhibited adipogenic activity; it mildly activated PPARγ levels in the liver and skeletal muscle. It also regulated insulin mediated glucose uptake in epididymal adipose tissue through translocation and activation of GLUT4 in PI3K/p-Akt signaling cascade. Embelin bound to PPARγ; it disclosed stable binding affinities to the active sites of PI3K, p-Akt and GLUT4.
  
  
  CONCLUSIONS
  These findings show that embelin could improve adipose tissue insulin sensitivity without increasing weight gain, enhance glycemic control, protect β-cell from damage and maintain glucose homeostasis in adipose tissue.
  
  
  CONCLUSIONS
  Embelin can be used in the prevention and treatment of type 2 diabetes mellitus caused due to obesity.
authors.affiliation: Entomology Research Institute, Loyola College, Chennai, India.
authors.forename: Gopalsamy Rajiv
authors.initials: GR
authors.lastname: Gandhi
authors.forename: Antony
authors.initials: A
authors.lastname: Stalin
authors.forename: Kedike
authors.initials: K
authors.lastname: Balakrishna
authors.forename: Savarimuthu
authors.initials: S
authors.lastname: Ignacimuthu
authors.forename: Michael Gabriel
authors.initials: MG
authors.lastname: Paulraj
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Vishal
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D016227:Benzoquinones / Q000737:chemistry / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D031645:Embelia / Q000737:chemistry; D005638:Fruit / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D008297:Male; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016227:Benzoquinones; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D047495:PPAR gamma; C495694:Slc2a4 protein, rat; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; C010945:embelin