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.

BACKGROUND Glucose intake has been shown to cause an increase in intranuclear nuclear factor-kappa B and a decrease in inhibitor kappa 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.

[1]  A. Aljada,et al.  Increase in intranuclear nuclear factor κB and decrease in inhibitor κB in mononuclear cells after a mixed meal: evidence for a proinflammatory effect , 2004 .

[2]  Michael F. Wilson,et al.  Anti-Inflammatory and Profibrinolytic Effect of Insulin in Acute ST-Segment–Elevation Myocardial Infarction , 2004, Circulation.

[3]  A. Aljada,et al.  Insulin suppresses plasma concentration of vascular endothelial growth factor and matrix metalloproteinase-9. , 2003, Diabetes care.

[4]  F. Cambien,et al.  Plasma Concentrations and Genetic Variation of Matrix Metalloproteinase 9 and Prognosis of Patients With Cardiovascular Disease , 2003, Circulation.

[5]  A. Aljada,et al.  Both lipid and protein intakes stimulate increased generation of reactive oxygen species by polymorphonuclear leukocytes and mononuclear cells. , 2002, The American journal of clinical nutrition.

[6]  A. Aljada,et al.  Insulin inhibits the pro-inflammatory transcription factor early growth response gene-1 (Egr)-1 expression in mononuclear cells (MNC) and reduces plasma tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) concentrations. , 2002, The Journal of clinical endocrinology and metabolism.

[7]  A. Aljada,et al.  Insulin Inhibits Intranuclear Nuclear Factor κB and Stimulates IκB in Mononuclear Cells in Obese Subjects: Evidence for an Anti-inflammatory Effect? , 2001 .

[8]  Valentin Fuster,et al.  Thrombus Formation on Atherosclerotic Plaques: Pathogenesis and Clinical Consequences , 2001, Annals of Internal Medicine.

[9]  Y. Nemerson,et al.  Circulating tissue factor and thrombosis , 2000, Current opinion in hematology.

[10]  A. Aljada,et al.  Glucose challenge stimulates reactive oxygen species (ROS) generation by leucocytes. , 2000, The Journal of clinical endocrinology and metabolism.

[11]  S. Seregard,et al.  Expression of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in inflammation-associated corneal neovascularization. , 2000, Experimental eye research.

[12]  D. Pinsky,et al.  Egr-1: is it always immediate and early? , 2000, The Journal of clinical investigation.

[13]  M. Cybulsky,et al.  High-level expression of Egr-1 and Egr-1-inducible genes in mouse and human atherosclerosis. , 2000, The Journal of clinical investigation.

[14]  P. Freskgård,et al.  Tissue factor-dependent factor VIIa signaling. , 2000, Trends in cardiovascular medicine.

[15]  H Wedel,et al.  Infarction : Long-Term Results From the Diabetes and Insulin-Glucose Infusion Conventionally Treated Patients With Diabetes Mellitus and Acute Myocardial Glycometabolic State at Admission : Important Risk Marker of Mortality in , 1999 .

[16]  L. Piegas,et al.  Metabolic Modulation of Acute Myocardial Infarction The ECLA Glucose-Insulin-Potassium Pilot Trial , 1998 .

[17]  W. Frishman,et al.  Matrix Metalloproteinases and Coronary Artery Disease: A Novel Therapeutic Target , 1997, Journal of clinical pharmacology.

[18]  Amyj . Williams,et al.  Inducible PDGF A-chain transcription in smooth muscle cells is mediated by Egr-1 displacement of Sp1 and Sp3. , 1997, The American journal of physiology.

[19]  G. Giannelli,et al.  Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5. , 1997, Science.

[20]  D. Steinberg,et al.  Lewis A. Conner Memorial Lecture. Oxidative modification of LDL and atherogenesis. , 1997, Circulation.

[21]  A. Charlesworth,et al.  William Heberden revisited: postprandial angina-interval between food and exercise and meal composition are important determinants of time to onset of ischemia and maximal exercise tolerance. , 1997, Journal of the American College of Cardiology.

[22]  E. Levin,et al.  Egr-1 Activates Basic Fibroblast Growth Factor Transcription , 1996, The Journal of Biological Chemistry.

[23]  J. Monroe,et al.  Role of EGR1 in regulation of stimulus-dependent CD44 transcription in B lymphocytes , 1996, Molecular and cellular biology.

[24]  J. Monroe,et al.  Transcriptional regulation of the Icam-1 gene in antigen receptor- and phorbol ester-stimulated B lymphocytes: role for transcription factor EGR1 , 1996, The Journal of experimental medicine.

[25]  Amyj . Williams,et al.  Egr-1-Induced Endothelial Gene Expression: A Common Theme in Vascular Injury , 1996, Science.

[26]  Amyj . Williams,et al.  Interplay of Sp1 and Egr-1 in the Proximal Platelet-derived Growth Factor A-Chain Promoter in Cultured Vascular Endothelial Cells (*) , 1995, The Journal of Biological Chemistry.

[27]  N. Mackman Regulation of the tissue factor gene , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[28]  G. Hensel,et al.  Characterization of an Krox-24/Egr-1-responsive element in the human tumor necrosis factor promoter. , 1994, Biochimica et biophysica acta.

[29]  V. Fuster,et al.  Atherogenesis and inflammation. , 1993, European heart journal.

[30]  W. Greene,et al.  Cross‐coupling of the NF‐kappa B p65 and Fos/Jun transcription factors produces potentiated biological function. , 1993, The EMBO journal.

[31]  T. Nakamura,et al.  Expression of the early growth response 1 and 2 zinc finger genes during induction of monocytic differentiation. , 1991, The Journal of clinical investigation.

[32]  N. Andrews,et al.  A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells. , 1991, Nucleic acids research.

[33]  R. Ross,et al.  Macrophage and smooth muscle cell proliferation in atherosclerotic lesions of WHHL and comparably hypercholesterolemic fat-fed rabbits. , 1990, Arteriosclerosis.

[34]  M. Sporn,et al.  Promoter sequences of the human transforming growth factor-beta 1 gene responsive to transforming growth factor-beta 1 autoinduction. , 1989, The Journal of biological chemistry.

[35]  N. Mackman,et al.  Complete sequence of the human tissue factor gene, a highly regulated cellular receptor that initiates the coagulation protease cascade. , 1989, Biochemistry.

[36]  P. Verde,et al.  An upstream enhancer and a negative element in the 5' flanking region of the human urokinase plasminogen activator gene. , 1988, Nucleic acids research.

[37]  G. V. Berghe,et al.  Intensive insulin therapy in critically ill patients. , 2001, The New England journal of medicine.

[38]  A. Aljada,et al.  Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect? , 2001, The Journal of clinical endocrinology and metabolism.

[39]  R. Diaz,et al.  Metabolic modulation of acute myocardial infarction. The ECLA (Estudios Cardiológicos Latinoamérica) Collaborative Group. , 1998, Circulation.

[40]  D. Steinberg Oxidative Modification of LDL and Atherogenesis , 1998 .

[41]  P. Dicorleto,et al.  Mechanisms of monocyte recruitment and accumulation. , 1993, British heart journal.