Abstract
Insulin-like growth factor 1 (IGF-1) stimulates cell proliferation and is crucial for
maintenance of somatic tissues. However, this effect is associated with the inhibition of
FOXO transcription factors and downregulation of antioxidative enzymes. In this study, we
compared the responses of primary dermal fibroblasts and human umbilical vein endothelial
cells with IGF-1 treatment. We found that IGF-1 primarily downregulated enzymatic
antioxidants in skin fibroblasts. However, human umbilical vein endothelial cells were
protected from an IGF-1–mediated decrease in antioxidative capacity. Moreover, IGF-1
also activated endothelial nitric oxide synthase in human umbilical vein endothelial
cells. These observations suggest a dichotomous role for IGF-1, which provides for growth
and repair needs of the soma, while attenuating the effect of oxidative stress on the
vasculature by activating endothelial nitric oxide synthase. This increases the production
of nitric oxide, an antiproliferative and, under certain circumstances, an antioxidant
agent. Findings could help clarify the role of IGF-1 in aging and longevity of lower
organisms, short-lived mammals, and humans.