Low Doses of Insulin Induce an Elastogenic Effect
HealthDay News—Insulin induces an elastogenic effect, with therapeutic doses of insulin stimulating the formation of elastic fibers in human aortic smooth muscle cell cultures, according to an experimental study published online Jan. 11 in The American Journal of Pathology.
Junyan Shi, of the Hospital for Sick Children in Toronto, and colleagues investigated whether insulin administered at therapeutically relevant concentrations (0.5–10nmol/L) would promote production of elastic fibers in laboratory cultures of human aortic smooth muscle cells.
The researchers found that the administration of insulin stimulated formation of new elastic fibers in human aortic smooth muscle cell cultures. There was no upregulation of collagen type I or fibronectin deposition, nor collagen stimulation. The elastogenic effect was found to occur after insulin receptor activation, which activated elastin gene transcription via a downstream phosphoinositide 3-kinase pathway. The promoter region of the human elastin gene contains a FoxO-recognized element, and following removal of the FoxO1 transcriptional inhibitor in the elastin gene promoter, the genomic effects of insulin occurred. Insulin signaling also facilitated the association of tropoelastin with its specific elastin-binding protein, which enhances secretion.
"We believe that our discovery of elastogenic action of insulin enables better understanding of the pathologic mechanisms by which the initial lack of insulin in type 1 diabetes or the insulin resistance in type 2 diabetes contribute to development of hypertension and the rapid progression of atherosclerosis," the authors write.