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- Title
c-Jun NH<sub>2</sub>-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.
- Authors
Sourris, Karly C.; Lyons, Jasmine G.; de Courten, Maximilian P. J.; Dougherty, Sonia L.; Henstridge, Darren C.; Cooper, Mark E.; Hage, Michelle; Dart, Anthony; Kingwell, Bronwyn A.; Forbes, Josephine M.; de Courten, Barbora
- 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. Diabetes 58:1259-1265, 2009
- Subjects
IMMUNE system; TYPE 2 diabetes; DIABETES complications; INSULIN resistance; OBESITY
- Publication
Diabetes, 2009, Vol 58, Issue 6, p1259
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db08-1725