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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

Representative immunoblots of human adipose tissue (n = 6) probed for total JNK (tJNK) and phosphorylated JNK (pJNK, Thr183/Tyr185).
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Figure 2: Representative immunoblots of human adipose tissue (n = 6) probed for total JNK (tJNK) and phosphorylated JNK (pJNK, Thr183/Tyr185).

Mentions: JNK1/2 activity in the adipose tissue was related to insulin sensitivity (r = −0.54, P < 0.05) (Fig. 2) before and after adjustment for age, sex, percent body fat, and WHR (P = 0.04). In stepwise regression with age, sex, percent body fat, and WHR, JNK1/2 activity in adipose tissue explained the 29% variance in insulin sensitivity (P = 0.02). When both JNK1/2 in adipose tissue and NF-κB activity in PBMCs were entered in the same model, only JNK1/2 activity in adipose tissue remained a significant determinant of insulin sensitivity, explaining 29% (P = 0.02), whereas percent body fat contributed 21% (P = 0.02) and sex 10% (P = 0.07). When forced into this model, NF-κB activity in PBMCs explained only 4% of the variance in insulin sensitivity (P = 0.1). JNK1/2 activity in PBMCs and muscle was not associated with any measures of obesity or glucose metabolism (all P> 0.2). Exclusion of the two subjects with impaired glucose metabolism (one with impaired glucose tolerance and one with impaired fasting glucose) did not significantly alter the correlations presented.


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)

Representative immunoblots of human adipose tissue (n = 6) probed for total JNK (tJNK) and phosphorylated JNK (pJNK, Thr183/Tyr185).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Representative immunoblots of human adipose tissue (n = 6) probed for total JNK (tJNK) and phosphorylated JNK (pJNK, Thr183/Tyr185).
Mentions: JNK1/2 activity in the adipose tissue was related to insulin sensitivity (r = −0.54, P < 0.05) (Fig. 2) before and after adjustment for age, sex, percent body fat, and WHR (P = 0.04). In stepwise regression with age, sex, percent body fat, and WHR, JNK1/2 activity in adipose tissue explained the 29% variance in insulin sensitivity (P = 0.02). When both JNK1/2 in adipose tissue and NF-κB activity in PBMCs were entered in the same model, only JNK1/2 activity in adipose tissue remained a significant determinant of insulin sensitivity, explaining 29% (P = 0.02), whereas percent body fat contributed 21% (P = 0.02) and sex 10% (P = 0.07). When forced into this model, NF-κB activity in PBMCs explained only 4% of the variance in insulin sensitivity (P = 0.1). JNK1/2 activity in PBMCs and muscle was not associated with any measures of obesity or glucose metabolism (all P> 0.2). Exclusion of the two subjects with impaired glucose metabolism (one with impaired glucose tolerance and one with impaired fasting glucose) did not significantly alter the correlations presented.

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