Glucose ingestion induces an increase in intranuclear nuclear factor κB, a fall in cellular inhibitor κB, and an increase in tumor necrosis factor α messenger RNA by mononuclear cells in healthy human subjects

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 KB (NF-KB) binding, the reduction of inhibitor kappa B a (I kappa B alpha) protein, and an increase in the activity of inhibitor KB kinase (IKK) and the expression of IKK alpha and IKK beta, the enzymes that phosphorylate I kappa BL alpha, in MNCs. Glucose intake caused an increase in NF-kappa B binding to NF-kappa B2, NF-kappa B2a, and NF-kappa B3 sequences in the promoter site of tumor necrosis factor a (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-kappa B binding, a fall in I kappa B alpha, an increase in IKK alpha, IKK beta, IKK beta activity, and messenger RNA expression of TNF-a in MNCs in healthy subjects. These data are consistent with profound acute pro-inflammatory changes in MNCs after glucose intake. (c) 2006 Elsevier Inc. All rights reserved.