Insulin resistance and endothelial dysfunction: A mutual relationship in cardiometabolic risk

Serena Del Turco, Melania Gaggini, Giuseppe Daniele, Giuseppina Basta, Franco Folli, Rosa Sicari, Amalia Gastaldelli

Research output: Contribution to journalReview articlepeer-review

24 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2420-2431
Number of pages12
JournalCurrent pharmaceutical design
Issue number13
StatePublished - May 21 2013


  • Cardiometabolic risk
  • Endothelial dysfunction
  • Insulin resistance
  • Insulin signaling pathways

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


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