title: Endothelial IGF-1 Receptor Signalling in Diabetes and Insulin Resistance.
abstract: 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.
authors.affiliation: Leeds Institute for Cardiovascular and Metabolic Medicine, LIGHT laboratories, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Cubbon
authors.affiliation: Leeds Institute for Cardiovascular and Metabolic Medicine, LIGHT laboratories, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK. Electronic address: m.t.kearney@leeds.ac.uk.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Kearney
authors.affiliation: Leeds Institute for Cardiovascular and Metabolic Medicine, LIGHT laboratories, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Wheatcroft
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D017526:Receptor, IGF Type 1
keywords: diabetes; endothelium; insulin resistance; insulin-like growth factor-1; vascular