File(s) under permanent embargo
Metallothionein 2a gene expression is increased in subcutaneous adipose tissue of type 2 diabetic patients
journal contribution
posted on 2013-01-01, 00:00 authored by V Haynes, Timothy ConnorTimothy Connor, A Tchernof, H Vidal, S DuboisSTUDY 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.
History
Journal
Molecular genetics and metabolismVolume
108Issue
1Pagination
90 - 94Publisher
ElsevierLocation
Waltham, Mass.Publisher DOI
ISSN
1096-7192eISSN
1096-7206Language
engPublication classification
C Journal article; C1.1 Refereed article in a scholarly journalCopyright notice
2012, ElsevierUsage metrics
Categories
No categories selectedKeywords
Insulin resistanceMetallothioneinGlucose uptakeAdipose TissueDiabetes Mellitus, Type 2HumansReactive Oxygen SpeciesReal-Time Polymerase Chain ReactionSubcutaneous FatScience & TechnologyLife Sciences & BiomedicineEndocrinology & MetabolismGenetics & HeredityMedicine, Research & ExperimentalResearch & Experimental MedicineTYROSINE-PHOSPHATASE 1BINSULIN-RESISTANCEZINCOBESITYMICEPOLYMORPHISMSMELLITUSAKT
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC