Glucose ingestion induces an increase in intranuclear nuclear factor kappaB, a fall in cellular inhibitor kappaB, and an increase in tumor necrosis factor alpha messenger RNA by mononuclear cells in healthy human subjects.
ABSTRACT Because hyperglycemia is a major detrimental factor in the prognosis of acute cardiovascular conditions such as acute myocardial infarction (AMI) and stroke, and because an acute glucose challenge in healthy subjects has been shown to induce oxidative stress in mononuclear cells (MNCs), we have now investigated whether glucose induces inflammatory stress at the cellular and molecular level. Glucose ingestion (75 g in 300 mL water) in healthy human subjects resulted in an increase in intranuclear nuclear factor kappaB (NF-kappaB) binding, the reduction of inhibitor kappaB alpha (IkappaBalpha) protein, and an increase in the activity of inhibitor kappaB kinase (IKK) and the expression of IKKalpha and IKKbeta, the enzymes that phosphorylate IkappaBalpha, in MNCs. Glucose intake caused an increase in NF-kappaB binding to NF-kappaB2, NF-kappaB2a, and NF-kappaB3 sequences in the promoter site of tumor necrosis factor alpha (TNF-alpha) gene along with an increase in the expression of TNF-alpha messenger RNA in MNCs. Membranous p47(phox) subunit, an index of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression and activation, also increased after glucose intake. We conclude that glucose intake induces an immediate increase in intranuclear NF-kappaB binding, a fall in IkappaBalpha, an increase in IKKalpha, IKKbeta, IKK activity, and messenger RNA expression of TNF-alpha in MNCs in healthy subjects. These data are consistent with profound acute pro-inflammatory changes in MNCs after glucose intake.
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ABSTRACT: To investigate the association of plasma levels of methylglyoxal (MG) and markers of inflammation/endothelial dysfunction with diabetic nephropathy (DN). Plasma levels of MG, cytokines, and adhesion molecules were measured in type 2 diabetic patients (T2DM), T2DM patients with DN, and the controls. Plasma MG levels in DN were significantly higher than those in T2DM and the controls (312 ± 135 vs. 212 ± 73 and 312 ± 135 vs. 147 ± 78 nmol/L, respectively, P<0.001). The plasma levels of MG were positively correlated with the fasting glucose, HbA1c, and urinary albumin/creatinine ratio (r=0.754, P<0.05). Plasma levels of IL-6, TNF-α, and adhesion molecules were markedly increased in DN compared to T2DM patients and the controls. Increased plasma levels of MG, cytokines, and adhesion molecules are associated with DN. These markers may be useful in predicting the development of DN.Clinical biochemistry 03/2011; 44(4):307-11. DOI:10.1016/j.clinbiochem.2010.11.004 · 2.23 Impact Factor