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Glucose intake induces an increase in activator protein 1 and early growth response 1 binding activities, in the expression of tissue factor and matrix metalloproteinase in mononuclear cells, and in plasma tissue factor and matrix metalloproteinase concentrations^1,2,3

¹ From the Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, and Kaleida Health, Buffalo

Background: Glucose intake has been shown to cause an increase in intranuclear nuclear factor-B and a decrease in inhibitor B that are consistent with a proinflammatory effect. We investigated the effect of glucose intake on 2 other proinflammatory transcription factors, activator protein 1 (AP-1) and early growth response 1 (Egr-1), and on the genes regulated by them, ie, the genes for matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) and tissue factor (TF), respectively.

Objective: The objective of the study was to ascertain whether the intake of 75 g glucose induces an increase in AP-1, Egr-1, and the genes regulated by them.

Design: Eight healthy subjects were given 75 g glucose dissolved in 300 mL water to drink. Blood samples were collected before and 1, 2, and 3 h after glucose intake. Four weeks later, the same subjects were given 300 mL water sweetened with saccharine, and blood samples were collected at the same time points. Mononuclear cells (MNCs) were separated, and nuclear fractions were isolated.

Results: AP-1 and Egr-1 binding activities were significantly higher 1 and 2 h after glucose intake and then decreased toward the baseline by 3 h. The expression of MMP-2 and TF in MNC homogenates also was significantly higher at 2 and 3 h. Plasma concentrations of MMP-2 were significantly higher at 3 h, whereas those of MMP-9 were significantly higher at 1, 2, and 3 h. In addition, TF was significantly higher at 2 and 3 h. Intake of saccharine-sweetened water had no significant effect on the inflammatory mediators measured in this study.

Conclusion: Glucose induces proinflammatory changes, including increases in AP-1, Egr-1, MMPs, and TF, the factors that regulate processes that are potentially relevant to atherosclerotic plaque rupture and thrombosis.

Key Words: Glucose • inflammation • activator protein 1 • early growth response 1 • matrix metalloproteinase 2 • matrix metalloproteinase 9 • tissue factor

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