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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.

Sourris KC, Lyons JG, de Courten MP, Dougherty SL, Henstridge DC, Cooper ME, Hage M, Dart A, Kingwell BA, Forbes JM, de Courten B - Diabetes (2009)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.

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-kappaB (NF-kappaB) 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-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.

Results: 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).

Conclusions: JNK1/2 activity in adipose tissue but not NF-kappaB activity in PBMCs is an independent determinant of insulin resistance in healthy individuals.

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Related in: MedlinePlus

NF-κB p65 activity in PBMCs and central obesity, insulin sensitivity, and JNK1 activity in subcutaneous adipose tissue and insulin sensitivity. A: NF-κB p65 activity in PBMCs and WHR. B: NF-κB p65 activity in PBMCs and total body fat. C: NF-κB p65 activity in PBMCs and M. D: JNK1/2 activity and insulin sensitivity (M).
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Figure 1: NF-κB p65 activity in PBMCs and central obesity, insulin sensitivity, and JNK1 activity in subcutaneous adipose tissue and insulin sensitivity. A: NF-κB p65 activity in PBMCs and WHR. B: NF-κB p65 activity in PBMCs and total body fat. C: NF-κB p65 activity in PBMCs and M. D: JNK1/2 activity and insulin sensitivity (M).

Mentions: NF-κB activity in either PBMCs or skeletal muscle was not associated with an overall measure of obesity, percent body fat (Table 3,Fig. 1). NF-κB activity in subcutaneous adipose tissue also was not related to any of the anthropometric variables. Furthermore, the gene expression of IκBα and NF-κB (p65) in PBMC did not correlate with any of the anthropometric or metabolic parameters or NF-κB activity in PBMCs (data not shown). However, we found that NF-κB activity in both PBMCs and skeletal muscle was positively associated with WHR (r = 0.48, P = 0.02; r = 0.68, P = 0.003) (Table 3,Fig. 1) before and after adjustment for age and sex (both P < 0.05). This association persisted after additional adjustment for percent body fat (both P < 0.05). Tissue JNK1/2 activity was not related to any measures of obesity (both P> 0.1) (Table 3).


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.

Sourris KC, Lyons JG, de Courten MP, Dougherty SL, Henstridge DC, Cooper ME, Hage M, Dart A, Kingwell BA, Forbes JM, de Courten B - Diabetes (2009)

NF-κB p65 activity in PBMCs and central obesity, insulin sensitivity, and JNK1 activity in subcutaneous adipose tissue and insulin sensitivity. A: NF-κB p65 activity in PBMCs and WHR. B: NF-κB p65 activity in PBMCs and total body fat. C: NF-κB p65 activity in PBMCs and M. D: JNK1/2 activity and insulin sensitivity (M).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2682665&req=5

Figure 1: NF-κB p65 activity in PBMCs and central obesity, insulin sensitivity, and JNK1 activity in subcutaneous adipose tissue and insulin sensitivity. A: NF-κB p65 activity in PBMCs and WHR. B: NF-κB p65 activity in PBMCs and total body fat. C: NF-κB p65 activity in PBMCs and M. D: JNK1/2 activity and insulin sensitivity (M).
Mentions: NF-κB activity in either PBMCs or skeletal muscle was not associated with an overall measure of obesity, percent body fat (Table 3,Fig. 1). NF-κB activity in subcutaneous adipose tissue also was not related to any of the anthropometric variables. Furthermore, the gene expression of IκBα and NF-κB (p65) in PBMC did not correlate with any of the anthropometric or metabolic parameters or NF-κB activity in PBMCs (data not shown). However, we found that NF-κB activity in both PBMCs and skeletal muscle was positively associated with WHR (r = 0.48, P = 0.02; r = 0.68, P = 0.003) (Table 3,Fig. 1) before and after adjustment for age and sex (both P < 0.05). This association persisted after additional adjustment for percent body fat (both P < 0.05). Tissue JNK1/2 activity was not related to any measures of obesity (both P> 0.1) (Table 3).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.

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-kappaB (NF-kappaB) 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-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.

Results: 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).

Conclusions: JNK1/2 activity in adipose tissue but not NF-kappaB activity in PBMCs is an independent determinant of insulin resistance in healthy individuals.

Show MeSH
Related in: MedlinePlus