Metallothionein 2a gene expression is increased in subcutaneous adipose tissue of type 2 diabetic patients

Haynes, Vanessa, Connor, Timothy, Tchernof, Andre, Vidal, Hubert and Dubois, Severine 2013, Metallothionein 2a gene expression is increased in subcutaneous adipose tissue of type 2 diabetic patients, Molecular genetics and metabolism, vol. 108, no. 1, pp. 90-94, doi: 10.1016/j.ymgme.2012.10.012.

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Title Metallothionein 2a gene expression is increased in subcutaneous adipose tissue of type 2 diabetic patients
Author(s) Haynes, Vanessa
Connor, Timothy
Tchernof, Andre
Vidal, Hubert
Dubois, Severine
Journal name Molecular genetics and metabolism
Volume number 108
Issue number 1
Start page 90
End page 94
Total pages 5
Publisher Elsevier
Place of publication Waltham, Mass.
Publication date 2013-01
ISSN 1096-7192
Keyword(s) Insulin resistance
Glucose uptake
Adipose Tissue
Diabetes Mellitus, Type 2
Reactive Oxygen Species
Real-Time Polymerase Chain Reaction
Subcutaneous Fat
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
Genetics & Heredity
Medicine, Research & Experimental
Research & Experimental Medicine
Summary STUDY 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.
Language eng
DOI 10.1016/j.ymgme.2012.10.012
Field of Research 110399 Clinical Sciences not elsewhere classified
1103 Clinical Sciences
Socio Economic Objective 920104 Diabetes
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2012, Elsevier
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Document type: Journal Article
Collection: Faculty of Health
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