TY - JOUR
T1 - Insulin resistance and endothelial dysfunction
T2 - A mutual relationship in cardiometabolic risk
AU - Del Turco, Serena
AU - Gaggini, Melania
AU - Daniele, Giuseppe
AU - Basta, Giuseppina
AU - Folli, Franco
AU - Sicari, Rosa
AU - Gastaldelli, Amalia
PY - 2013/5/21
Y1 - 2013/5/21
N2 - 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.
AB - 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.
KW - Cardiometabolic risk
KW - Endothelial dysfunction
KW - Insulin resistance
KW - Insulin signaling pathways
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U2 - 10.2174/1381612811319130010
DO - 10.2174/1381612811319130010
M3 - Review article
C2 - 23173591
AN - SCOPUS:84877822919
VL - 19
SP - 2420
EP - 2431
JO - Current Pharmaceutical Design
JF - Current Pharmaceutical Design
SN - 1381-6128
IS - 13
ER -