title: Opposite effects of genistein on the regulation of insulin-mediated glucose homeostasis in adipose tissue.
abstract: OBJECTIVE
  Genistein is an isoflavone phytoestrogen found in a number of plants such as soybeans and there is accumulating evidence that it has beneficial effects on the regulation of glucose homeostasis. In this study we evaluated the effect of genistein on glucose homeostasis and its underlying mechanisms in normal and insulin-resistant conditions.
  
  
  METHODS
  To induce insulin resistance, mice or differentiated 3T3-L1 adipocytes were treated with macrophage-derived conditioned medium. A glucose tolerance test was used to investigate the effect of genistein. Insulin signalling activation, glucose transporter-4 (GLUT4) translocation and AMP-activated PK (AMPK) activation were detected by Western blot analysis or elisa.
  
  
  RESULTS
  Genistein impaired glucose tolerance and attenuated insulin sensitivity in normal mice by inhibiting the insulin-induced phosphorylation of insulin receptor substrate-1 (IRS1) at tyrosine residues, leading to inhibition of insulin-mediated GLUT4 translocation in adipocytes. Mac-CM, an inflammatory stimulus induced glucose intolerance accompanied by impaired insulin sensitivity; genistein reversed these changes by restoring the disturbed IRS1 function, leading to an improvement in GLUT4 translocation. In addition, genistein increased AMPK activity under both normal and inflammatory conditions; this was shown to contribute to the anti-inflammatory effect of genistein, which leads to an improvement in insulin signalling and the amelioration of insulin resistance.
  
  
  CONCLUSIONS
  Genistein showed opposite effects on insulin sensitivity under normal and inflammatory conditions in adipose tissue and this action was derived from its negative or positive regulation of IRS1 function. Its up-regulation of AMPK activity contributes to the inhibition of inflammation implicated in insulin resistance.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, China.
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.forename: X J
authors.initials: XJ
authors.lastname: Gao
authors.forename: W W
authors.initials: WW
authors.lastname: Zhao
authors.forename: W J
authors.initials: WJ
authors.lastname: Zhao
authors.forename: C H
authors.initials: CH
authors.lastname: Jiang
authors.forename: F
authors.initials: F
authors.lastname: Huang
authors.forename: J P
authors.initials: JP
authors.lastname: Kou
authors.forename: B L
authors.initials: BL
authors.lastname: Liu
authors.forename: K
authors.initials: K
authors.lastname: Liu
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010766:Phosphorylation / Q000187:drug effects; D048789:Phytoestrogens / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D051275:Glucose Transporter Type 4; D007328:Insulin; D048789:Phytoestrogens; D019833:Genistein; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: AMP-activated PK; adipocyte; genistein; inflammation; insulin resistance