TNF-α levels are associated with skin capillary recruitment in humans: a potential explanation for the relationship between TNF-α and insulin resistance

2006 ◽  
Vol 110 (3) ◽  
pp. 361-368 ◽  
Author(s):  
Richard G. Ijzerman ◽  
Jasper J. Voordouw ◽  
Mirjam M. Van Weissenbruch ◽  
John S. Yudkin ◽  
Erik H. Serné ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Α ◽  
Capillary Recruitment ◽  
Tnf Α ◽  
Factor Α ◽  
Sandwich Enzyme Immunoassay ◽  
The Relationship ◽  
Necrosis Factor

The mechanism by which TNF-α (tumour necrosis factor-α) may cause insulin resistance is not clear. On the basis of experiments in rats, TNF-α has been suggested to cause defects in capillary function, with a decreased access of insulin and glucose to tissues. To test this hypothesis in humans, we assessed serum TNF-α concentrations, skin capillary recruitment and insulin sensitivity in a group of 37 healthy adults. In addition, we measured these variables in 21 of their prepubertal children. Serum TNF-α levels were measured by sandwich enzyme immunoassay, and insulin sensitivity was assessed with the hyperinsulinaemic euglycaemic clamp technique. Capillary recruitment during post-occlusive reactive hyperaemia was evaluated by videomicroscopy. In the adults, serum TNF-α levels were associated with both capillary recruitment (r=−0.40, P=0.02) and insulin sensitivity (r=−0.33, P=0.05). In addition, capillary recruitment was associated with insulin sensitivity (r=0.34, P=0.04). Regression analysis showed that the association between TNF-α and insulin sensitivity [−0.527 mg·kg−1 of body weight·min−1 per pmol/l per pg/ml TNF-α (95% confidence interval, −1.066 to 0.011); P=0.05] decreased by 30% after adjustment for capillary recruitment. In the children, neither capillary recruitment (r=0.33, P=0.2) nor insulin sensitivity (r=−0.24, P=0.4) was significantly associated with TNF-α. In conclusion, in adults, but not in children, serum TNF-α levels are associated with capillary recruitment during post-occlusive hyperaemia, which, in part, can explain the relationship between TNF-α and insulin resistance. Our data suggest that these relationships are initiated during growth from childhood to adulthood.

Effects of tumour necrosis factor-α and inhibition of protein kinase C on glucose uptake in L6 myoblasts

2000 ◽  
Vol 99 (4) ◽  
pp. 303-307 ◽  
Author(s):  
Divina PATIAG ◽  
Samuel GRAY ◽  
Iskander IDRIS ◽  
Richard DONNELLY
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase C ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Α ◽  
Kinase C ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Clinical and experimental studies have implicated high circulating levels of the cytokine tumour necrosis factor-α (TNF-α) in the pathogenesis of insulin resistance, not only in obesity and diabetes, but also in clinical conditions associated with cachexia and sepsis. TNF-α impairs insulin-mediated glucose uptake in adipocytes, but because of lipolytic effects the interpretation of clinical studies and the extent to which TNF-α affects muscle insulin sensitivity are unclear. In addition, protein kinase C (PKC) has recently been implicated in the mechanism of TNF-α-induced insulin resistance. The present study investigated the effects of TNF-α and a PKC inhibitor (RO-318220) on basal and insulin-stimulated 2-[3H]deoxyglucose uptake in cultured L6 myoblasts. Reverse transcriptase–PCR analysis confirmed that L6 myoblasts express TNF-α receptors I and II (p60 and p80). Dose–response curves for glucose uptake were fitted to a quadratic function to derive CI-150 values (concentration of insulin required to increase glucose uptake by 50%). Incubation with TNF-α at 1 or 10 ng/ml for 24 h had no significant effect on basal glucose uptake, insulin sensitivity or maximal insulin responsiveness. CI-150 values (means±S.E.M.) were as follows: basal, 91.2±13 nM; 1 ng/ml TNF-α, 102±12 nM; and basal, 70.8±13 nM; 10 ng/ml TNF-α, 43.7±40 nM. PKC inhibition markedly attenuated glucose uptake, but there was no difference in insulin sensitivity with RO-318220 alone compared with RO-318220+TNF-α. In conclusion, although increased TNF-α expression and plasma concentrations have been implicated in the pathogenesis of insulin resistance in various clinical states, there is no evidence that TNF-α impairs insulin-stimulated glucose uptake in a skeletal-muscle-derived cell line.

scholarly journals Down-regulation of cyclic-nucleotide phosphodiesterase 3B in 3T3-L1 adipocytes induced by tumour necrosis factor α and cAMP

2000 ◽  
Vol 346 (2) ◽  
pp. 337-343 ◽  
Author(s):  
Tova RAHN LANDSTRÖM ◽  
Jie MEI ◽  
Marie KARLSSON ◽  
Vincent MANGANIELLO ◽  
Eva DEGERMAN
Keyword(s):  
Insulin Resistance ◽  
Tumour Necrosis Factor ◽  
Cyclic Nucleotide ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Α ◽  
Down Regulation ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

We have used murine 3T3-L1 cells, which differentiate in culture and acquire morphological and biochemical features of mature adipocytes, as a model for studying the expression of cyclic-nucleotide phosphodiesterase (PDE) 3B activity, protein and mRNA during differentiation and during long-term treatment of the cells with tumour necrosis factor α (TNF-α), a cytokine associated with insulin resistance, and a cAMP analogue, N6,2ʹ-O-dibutyryl cAMP (dbcAMP). PDE3B activity, protein and mRNA could be detected 4 days after the initiation of differentiation of 3T3-L1 preadipocytes. Treatment of 3T3-L1 adipocytes with 10 ng/ml TNF-α for 24 h produced a maximal (50%) decrease in PDE3B activity, protein and mRNA, which was well correlated with both activation of protein kinase A (PKA) and stimulation of lipolysis, presumably reflecting an increase in intracellular cAMP concentration. To investigate the effect of cAMP on PDE3B we treated 3T3-L1 adipocytes with dbcAMP. After 4 h with 0.5 mM dbcAMP, PDE3B activity was decreased by 80%, which was also correlated with a decrease in PDE3B protein and mRNA. This effect was abolished in the presence of N-[2-(bromocinnamylamino)ethyl]-5-isoquinolinesulphonamide] (H-89), a specific PKA inhibitor. We conclude that the lipolytic effect of TNF-α involves the down-regulation of PDE3B, which is associated with increased activation of PKA, presumably owing to increased levels of cAMP. In addition, the PKA activation induced by dbcAMP resulted in the down-regulation of PDE3B. These results, which suggest that PDE3B is a novel target for long-term regulation by TNF-α and cAMP, could contribute to the understanding of the mechanisms of insulin resistance.

Differential effect of selective block of α2-adrenoreceptors on plasma levels of tumour necrosis factor-α, interleukin-6 and corticosterone induced by bacterial lipopolysaccharide in mice

1995 ◽  
Vol 144 (3) ◽  
pp. 457-462 ◽  
Author(s):  
G Haskó ◽  
I J Elenkov ◽  
V Kvetan ◽  
E S Vizi
Keyword(s):  
Tumour Necrosis Factor ◽  
Interleukin 6 ◽  
Plasma Levels ◽  
Tumour Necrosis ◽  
Endotoxin Shock ◽  
Bacterial Lipopolysaccharide ◽  
Tumour Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Abstract The effect of selective block of α2-adrenoreceptors on plasma levels of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and corticosterone induced by bacterial lipopolysaccharide (LPS) was investigated in mice using ELISA and RIA. It was found that the LPS-induced TNF-α response was significantly blunted in mice pretreated with CH-38083, a novel and highly selective α2-adrenoreceptor antagonist (the α2/α1 ratio is >2000). In contrast, LPS-induced increases in both corticosterone and IL-6 plasma levels were further increased by CH-38083. Since it has recently been shown that the selective block of α2-adrenoreceptors located on noradrenergic axon terminals resulted in an increase in the release of noradrenaline (NA), both in the central and peripheral nervous systems, and, in our experiments, that propranolol prevented the effect of α2-adrenoreceptor blockade on TNF-α plasma levels induced by LPS, it seems likely that the excessive stimulation by NA of β-adrenoreceptors located on cytokine-secreting immune cells is responsible for this action. Since it is generally accepted that increased production of TNF-α is involved in the pathogenesis of inflammation and endotoxin shock on the one hand, and corticosterone and even IL-6 are known to possess anti-inflammatory properties on the other hand, it is suggested that the selective block of α2-adrenoreceptors might be beneficial in the treatment of inflammation and/or endotoxin shock. Journal of Endocrinology (1995) 144, 457–462

scholarly journals Intracellular NAD+ levels are associated with LPS-induced TNF-α release in pro-inflammatory macrophages

2016 ◽  
Vol 36 (1) ◽  
Author(s):  
Abbas Jawad Al-Shabany ◽  
Alan John Moody ◽  
Andrew David Foey ◽  
Richard Andrew Billington
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Inflammatory Cytokine ◽  
Bacterial Lipopolysaccharide ◽  
Tumour Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Inflammatory Macrophages ◽  
Inflammatory Macrophage ◽  
Necrosis Factor

Bacterial lipopolysaccharide induces changes in intracellular NAD+ levels in a pro-inflammatory, but not an anti-inflammatory, macrophage model that are correlated with the release of the pro-inflammatory cytokine tumour necrosis factor-α (TNF-α).

Sign in / Sign up

Export Citation Format

Share Document