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133325 - c-Jun NH2-terminal kinase activity in subcutaneous adipose tissue but not nuclear factor-kB.pdf (146.73 kB)

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

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posted on 2023-05-20, 04:41 authored by Sourris, KC, Lyons, JG, de Courten, MPJ, Dougherty, SL, Darren HenstridgeDarren Henstridge, Cooper, ME, Hage, M, Dart, A, Kingwell, BA, Forbes, JM, de Courten, B

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.

History

Publication title

Diabetes

Volume

58

Issue

6

Pagination

1259-1265

ISSN

0012-1797

Department/School

School of Health Sciences

Publisher

Amer Diabetes Assoc

Place of publication

1701 N Beauregard St, Alexandria, USA, Va, 22311-1717

Rights statement

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/

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified