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c-Jun NH2-Terminal Kinase Activity in Subcutaneous Adipose Tissue but Not Nuclear Factor-κB Activity in Peripheral Blood Mononuclear Cells Is an Independent Determinant of Insulin Resistance in Healthy Individuals

Sourris, Karly C, Lyons, Jasmine G, de Courten, Maximilian, Dougherty, Sonia L, Henstridge, D. C, Cooper, Mark E, Hage, M, Dart, A, Kingwell, Bronwyn A, Forbes, Josephine M and de Courten, Barbora (2009) c-Jun NH2-Terminal Kinase Activity in Subcutaneous Adipose Tissue but Not Nuclear Factor-κB Activity in Peripheral Blood Mononuclear Cells Is an Independent Determinant of Insulin Resistance in Healthy Individuals. Diabetes, 58 (6). pp. 1259-1265. ISSN 0012-1797 (print) 1939-327X (online)

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Abstract

OBJECTIVE Chronic low-grade activation of the immune system (CLAIS) predicts type 2 diabetes via a decrease in insulin sensitivity. Our study investigated potential relationships between nuclear factor-κB (NF-κB) and c-Jun NH2-terminal kinase (JNK) pathways—two pathways proposed as the link between CLAIS and insulin resistance. RESEARCH DESIGN AND METHODS Adiposity (dual-energy X-ray absorptiometry), waist-to-hip ratio (WHR), and insulin sensitivity (M, hyperinsulinemic-euglycemic clamp) were measured in 22 healthy nondiabetic volunteers (aged 29 ± 11 years, body fat 28 ± 11%). NF-κB activity (DNA-binding assay) and JNK1/2 activity (phosphorylated JNK) were assessed in biopsies of the vastus lateralis muscle and subcutaneous adipose tissue and in peripheral blood mononuclear cell (PBMC) lysates. RESULTS NF-κB activities in PBMCs and muscle were positively associated with WHR after adjustment for age, sex, and percent body fat (both P < 0.05). NF-κB activity in PBMCs was inversely associated with M after adjustment for age, sex, percent body fat, and WHR (P = 0.02) and explained 16% of the variance of M. There were no significant relationships between NF-κB activity and M in muscle or adipose tissue (both NS). Adipose-derived JNK1/2 activity was not associated with obesity (all P> 0.1), although it was inversely related to M (r = −0.54, P < 0.05) and explained 29% of its variance. When both NF-κB and JNK1/2 were examined statistically, only JNK1/2 activity in adipose tissue was a significant determinant of insulin resistance (P = 0.02). CONCLUSIONS JNK1/2 activity in adipose tissue but not NF-κB activity in PBMCs is an independent determinant of insulin resistance in healthy individuals

Item Type: Article
Uncontrolled Keywords: JNK, NF-κB activity, CLAIS, insulin resistance, obesity, PBMCs, type 2 diabetes
Subjects: FOR Classification > 1103 Clinical Sciences
Faculty/School/Research Centre/Department > College of Health and Biomedicine
Depositing User: Ms Julie Gardner
Date Deposited: 08 Jul 2014 06:13
Last Modified: 30 Aug 2016 00:16
URI: http://vuir.vu.edu.au/id/eprint/25491
DOI: https://doi.org/10.2337/db08-1725
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Citations in Scopus: 25 - View on Scopus

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