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Insulin-like growth factor-1 receptor expression masks the antiinflammatory and glucose uptake capacity of insulin in vascular smooth muscle cells.


ABSTRACT:

Objective

Insulin resistance of vascular smooth muscle cells (VSMCs) has been linked to accelerated atherosclerosis in diabetes; however, the effects of insulin on VSMCs remain controversial. Most VSMC insulin receptors are sequestered into insulin-insensitive hybrids with insulin-like growth factor-1 receptors (IGF1Rs). Thus we hypothesized that regulation of IGF1R expression may impact cellular insulin sensitivity.

Methods and results

IGF1R expression was increased in aortas from diabetic mice. IGF1R overexpression in VSMCs impaired insulin-induced Akt phosphorylation. Conversely, IGF1R downregulation by siRNA allowed assembly of insulin holoreceptors, enhanced insulin-induced phosphorylation of its receptor, Akt, Erk1/2, and further augmented insulin-induced glucose uptak

SUBMITTER: Engberding N 

PROVIDER: S-EPMC2713108 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature