title: Insulin resistance and endothelial dysfunction: a mutual relationship in cardiometabolic risk.
abstract: Cardiometabolic risk comprises a cluster of traditional and emerging factors that are good indicators of a patient's overall risk for type 2 diabetes and cardiovascular disease. The insulin resistance, a key feature common to obesity and type 2 diabetes, is associated with impaired vascular response and contributes to increased cardiovascular risk. Abnormal vascular insulin signalling induces endothelial dysfunction, the initial step of atherosclerotic process, characterized by attenuated nitric oxide-mediated vasodilatation and atherogenic response. Insulin resistance and endothelial dysfunction are two pathological conditions that can co-exist, even if their cause-effect relationship is not yet clarified. Multiple signaling pathways shared by insulin resistance and endothelial dysfunction include hyperinsulinemia, glucotoxicity, lipotoxicity, and inflammation. These mechanisms selectively impair PI3K-dependent insulin in vascular endothelium harming endothelial balance and strengthening the evidence of the close association between metabolic and cardiovascular disease. The present review analyzes the close relationship between endothelial dysfunction and insulin resistance and explores the common mechanisms, with clinical considerations and pharmacological strategies.
authors.affiliation: Institute of Clinical Physiology, National Research Council, Pisa, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Del Turco
authors.forename: Melania
authors.initials: M
authors.lastname: Gaggini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Daniele
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Basta
authors.forename: Franco
authors.initials: F
authors.lastname: Folli
authors.forename: Rosa
authors.initials: R
authors.lastname: Sicari
authors.forename: Amalia
authors.initials: A
authors.lastname: Gastaldelli
mesh_terms: D002318:Cardiovascular Diseases / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008019:Life Style; D008659:Metabolic Diseases / Q000503:physiopathology*; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D007328:Insulin