title: Metallothionein 2a gene expression is increased in subcutaneous adipose tissue of type 2 diabetic patients.
abstract: BACKGROUND
  Insulin resistance plays an important role in the pathogenesis of type 2 diabetes and the metabolic syndrome. Many of the genes and pathways involved have been identified but some remain to be defined. Metallothioneins (Mts) are a family of anti-oxidant proteins and metallothionein 2a (Mt2a) polymorphims have been recently associated with type 2 diabetes and related complications. Our objective was to determine the Mt2a gene expression levels in adipose tissues from diabetic patients and the effect of Mt treatment on adipocyte insulin sensitivity.
  
  
  METHODS
  Samples of subcutaneous and visceral adipose tissues from lean, type 2 diabetic and non-diabetic obese patients were analysed using RT-qPCR for Mt2a mRNA abundance. The regulation of Mt2a expression was further studied in 3T3-L1 adipocytes treated or not with TNFα (10 ng/ml, 72 h) to induce insulin resistance. The effects of Mt on glucose uptake were investigated in cultured adipocytes treated with recombinant Mt protein.
  
  
  RESULTS
  We found that the Mt2a gene expression was significantly higher in adipose tissue of type 2 diabetic patients in comparison to that of lean (p=0.003) subjects. In 3T3-L1 adipocytes, insulin resistance induced by TNFα increased Mt2a mRNA levels (p=3×10(-4)) and insulin-stimulated glucose uptake was significantly inhibited by 53% (p=8×10(-4)) compared to vehicle, when 3T3-L1 adipocytes were treated with Mt protein.
  
  
  CONCLUSIONS
  These data suggest that Mt2a might be involved in insulin resistance through the up-regulation of Mt gene expression, which may lead to the modulation of insulin action in fat cells. These results suggest the concept of considering Mt proteins as markers and potential targets in type 2 diabetes.
authors.affiliation: Metabolic Research Unit, Deakin University, Geelong, Australia.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Haynes
authors.forename: Timothy
authors.initials: T
authors.lastname: Connor
authors.forename: Andre
authors.initials: A
authors.lastname: Tchernof
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.forename: Severine
authors.initials: S
authors.lastname: Dubois
mesh_terms: D000273:Adipose Tissue / Q000201:enzymology* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance; D008668:Metallothionein / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D050151:Subcutaneous Fat / Q000201:enzymology* / Q000378:metabolism
chemical_list: C491053:MT2A protein, human; D017382:Reactive Oxygen Species; D008668:Metallothionein