Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York 14209
Abstract
In view of our recent demonstration that insulin inhibits the
expression of intercellular adhesion molecule-1 (ICAM-1) and the fact
that ICAM-1 expression is known to be modulated by nuclear factor-B
(NF
B), we have now investigated whether insulin inhibits
intranuclear NF
B binding activity. We have also investigated whether
insulin inhibits the pro-inflammatory chemokine, monocyte
chemoattractant protein-1 (MCP-1), which attracts leucocytes to the
inflamed sites and is also regulated by NF
B. Insulin was incubated
with cultured human aortic endothelial cells (HAEC) at 0, 100 and 1000
µU/mL. Intranuclear NF
B binding activity was suppressed by
approximately 45% at 100 µU/mL and by 60% at 1000 µU/mL (p
< 0.05). MCP-1 mRNA expression was also suppressed by 47% at 100
µU/mL and by 79% at 1000 µU/mL (p < 0.05). We conclude that
insulin at physiologically relevant concentrations exerts an inhibitory
effect on the cardinal pro-inflammatory transcription factor NF
B and
the pro-inflammatory chemokine MCP-1; these effects suggest an
anti-inflammatory and potential anti-atherogenic effects of insulin.