Sourris, KC and Lyons, JG and de Courten, MPJ and Dougherty, SL and Henstridge, DC and Cooper, ME and Hage, M and Dart, A and Kingwell, BA and Forbes, JM and de Courten, B, 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 (2009) [Refereed Article]
Copyright 2009 by the American Diabetes Association. Licensed under Creative Commons Attribution 3.0 Unported (CC BY 3.0) https://creativecommons.org/licenses/by/3.0/
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:||Refereed Article|
|Keywords:||I kappa B alpha, immunoglobulin enhancer binding protein, insulin, mitogen activated protein kinase 9, stress activated protein kinase 1, transcription factor RelA, immunoglobulin enhancer binding protein, mitogen activated protein kinase 9, adult|
|Research Division:||Biological Sciences|
|Research Group:||Biochemistry and cell biology|
|Research Field:||Cell metabolism|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Henstridge, DC (Mr Darren Henstridge)|
|Web of Science® Times Cited:||25|
|Deposited By:||Health Sciences|
|Downloads:||8 View Download Statistics|
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