We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
c-Jun NH2-terminal kinase activity in subcutaneous adipose tissue but not nuclear factor-kappaB activity in peripheral blood mononuclear cells is an independent determinant of insulin resistance in healthy individuals.
- Authors
Sourris KC; Lyons JG; de Courten MP; Dougherty SL; Henstridge DC; Cooper ME; Hage M; Dart A; Kingwell BA; Forbes JM; de Courten B; 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
- Abstract
<bold>Objective: </bold>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-kappaB (NF-kappaB) and c-Jun NH(2)-terminal kinase (JNK) pathways-two pathways proposed as the link between CLAIS and insulin resistance.<bold>Research Design and Methods: </bold>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-kappaB 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.<bold>Results: </bold>NF-kappaB activities in PBMCs and muscle were positively associated with WHR after adjustment for age, sex, and percent body fat (both P < 0.05). NF-kappaB 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-kappaB 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-kappaB and JNK1/2 were examined statistically, only JNK1/2 activity in adipose tissue was a significant determinant of insulin resistance (P = 0.02).<bold>Conclusions: </bold>JNK1/2 activity in adipose tissue but not NF-kappaB activity in PBMCs is an independent determinant of insulin resistance in healthy individuals.
- Publication
Diabetes, 2009, Vol 58, Issue 6, p1259
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db08-1725