Endothelial IGF-1 Receptor Signalling in Diabetes and Insulin Resistance

Despite contemporary medical therapy, people with diabetes and insulin resistance experience substantially increased risk of cardiovascular events caused by atherosclerosis. Dysfunction of the endothelium is a key phase in early atherogenesis and represents a promising therapeutic target. The evolutionarily related insulin and insulin-like growth factor-1 (IGF-1) axes are implicated in the development of vascular disease. In this review, we summarise recent developments in our understanding of how modulating the IGF-1 axis influences vascular disease in the setting of insulin resistance. By contrasting data from models of altered insulin and/or IGF-1 signalling, we emphasise the complex spatiotemporal interplay of these systems in health and disease. We then discuss therapeutic opportunities, before detailing important gaps in our knowledge relevant to therapeutic translation.

TrendsInsulin-resistant disorders are associated with endothelial dysfunction and atherosclerosis.Insulin and IGF-1 signalling are highly inter-related, due in part to their evolutionarily related cognate receptors forming hybrid receptors.Modulation of vascular IGF-1 signalling can mitigate the adverse vascular effects of insulin resistance.Spatiotemporal differences in IGF-1 signalling, along with distinct effects of ligand-versus receptor-targeted interventions, may be important considerations when developing therapeutic strategies.