c-Jun NH 2 -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
Karly C. Sourris 1 ,
Jasmine G. Lyons 1 ,
Maximilian P.J. de Courten 2 ,
Sonia L. Dougherty 1 ,
Darren C. Henstridge 1 ,
Mark E. Cooper 1 ,
Michelle Hage 3 ,
Anthony Dart 3 ,
Bronwyn A. Kingwell 1 ,
Josephine M. Forbes 1 and
Barbora de Courten 1
1 Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia;
2 School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia;
3 Department of Cardiology, Alfred Hospital, Melbourne, Victoria, Australia.
Corresponding author: Barbora de Courten, barbora.decourten{at}bakeridi.edu.au .
K.C.S. and J.G.L. contributed equally to this work.
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 NH 2 -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.
Footnotes
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Received December 11, 2008.
Accepted February 20, 2009.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work
is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
© 2009 by the American Diabetes Association....

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

10.2337/db08-1725