Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York 14209
Abstract
We have recently demonstrated that an infusion of a low dose of
insulin reduces the intranuclear NF-B (a pro-inflammatory
transcription factor) content in MNC while also reducing the p;asma
concentration of NF-
B 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.