On how insulin may influence ageing and become atherogenic throughout the insulin-like growth factor-1 receptor pathway: in vitro studies with human vascular smooth muscle cells.

Background: It is known that growth factors play a role in ageing and atherogenesis, and insulin develops mitogenic activity in vitro.

Objectives: This study focuses on the pathway by which insulin induces proliferation and mobility in vascular smooth muscle cells (SMCs) compared with that of insulin-like growth factor-1 (IGF-1), because they are two basic phenomena for atherogenesis that could also help to understand the role of insulin in the ageing process.

Methods: Bromodeoxyuridine DNA incorporation, chemotaxis and the appearance of membrane ruffles were measured in cultured SMCs after incubation with insulin or IGF-1 in the presence of insulin or IGF-1 receptor-blocking antibodies.

Results: Insulin-induced SMC proliferation through the IGF-1 receptors; indeed, the blockade of insulin receptors does not inhibit the mitogenic influence of insulin. On the contrary, insulin-induced cell migration was inhibited by blocking the insulin receptor but not the IGF-1 receptor. Nevertheless, in less differentiated SMCs from non-confluent cultures, the migratory response was significantly higher and insulin lost its receptor specificity. It was stimulated through receptors both for insulin and IGF-1. In these cases the IGF-1 action was similar. Insulin-induced F-actin rearrangements took place through both types of receptors, but IGF-1 was a little more specific through its own receptors.

Conclusion: The pathway activated by insulin to induce SMC proliferation is not different from that of IGF-1, whereas the unspecific mechanism inducing mobility in growing cells seems to be related to a higher sensitivity response. Cells with the highest mitotic activity have the highest mobility in which stimulation of receptor specificity is lost for either insulin or IGF-1. Extrapolating these results to in vivo, insulin could become relevant for inducing stabilization and also side effects in ageing.