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

• Published in: The journal of clinical endocrinology and metabolism Vol. 87; no. 3; pp. 1419 - 1422
• Main Authors: Aljada, Ahmad, Ghanim, Husam, Mohanty, Priya, Kapur, Neeti, Dandona, Paresh
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.03.2002; Endocrine Society
• Subjects: Adult; Biological and medical sciences; Blood Glucose - analysis; DNA-Binding Proteins - antagonists & inhibitors; Early Growth Response Protein 1; EGR-1 protein; Electrophoretic mobility; Enzyme-linked immunosorbent assay; Fibrinolysis; Hormones. Endocrine system; Humans; Immediate-Early Proteins; Inflammation; Insulin; Insulin - blood; Insulin - pharmacology; Leukocytes (mononuclear); Medical sciences; Metabolic diseases; Middle Aged; Monocytes - metabolism; NF-κB protein; Obesity; Osmolar Concentration; Pharmacology. Drug treatments; Plasma; Plasminogen Activator Inhibitor 1 - metabolism; Plasminogen activator inhibitors; Thrombin; Thromboplastin - antagonists & inhibitors; Thromboplastin - metabolism; Tissue factor; Transcription factors; Transcription Factors - antagonists & inhibitors; Obesity; Low dose; Nutrition disorder; Tissue factor; Concentration; Gene expression; Insulin; Blood plasma; Plasminogen activator inhibitor 1; Mononuclear cell; Early; Earliness; Transcription factor; ELISA assay; Nutritional status; Growth factor
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jcem.87.3.8462

We have recently demonstrated that an infusion of a low dose of insulin reduces the intranuclear NF-κB (a pro-inflammatory transcription factor) content in MNC while also reducing the p;asma concentration of NF-κB dependent pro-inflammatory cytokines and adhesion molecules. We have now tested the effect of insulin on the pro-inflammatory transcription factor, early growth response-1 (Egr-1) and plasma concentration of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1), two major proteins whose expression is modulated by Egr-1. Insulin was infused at the rate of 2 IU/h in 5% dextrose (100 mL/h) and KCI (8 mmol/h) for 4 h in the fasting state in ten obese subjects. Blood samples were obtained at 0, 2, 4 and 6 h. MNC were isolated and their total homogenates and nuclear fractions were prepared and Egr-1 was measured by electrophoretic mobility shift assay (EMSA). Plasma TF and PAI-1 were assayed by ELISA. There was a significant fall in Egr-1 at 2 (66 ± 14% of basal level) and 4 h (47± 17% of the basal level; P<0.01). PAI-1 levels (basal = 100%) decreased significantly after insulin infusion at 2 h (57 ± 6.7% of the basal level) and at 4 h (58 ± 8.3% of the basal level; P<0.001). Plasma TF levels (basal = 100%) decreased to 76 ± 7.7% of the basal level at 2 h and to 85 ± 10.4% of the basal level at 4 h (P<0.05). Thus, insulin reduces intranuclear Egr-1 and the expression of TF and PAI-1. These data provide further evidence that insulin has an anti-inflammatory effect including the inhibition of TF and PAI-1 expression. These effects suggest a potential beneficial effect of insulin in thrombin formation and fibrinolysis in atherothrombosis.