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

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