Glucose, insulin and potential strategies of vascular stiffening

Abstract

Hyperglycemia and hyperinsulinemia which are independent risk factors for vascular stiffening and diabetic vasculopathy are present in most patients with Type 2 diabetes mellitus. In this review we discuss these factors which promote vascular stiffness. We also discuss the roles of renin- angiotensin II -aldosterone (RAAS) activation, obesity, hypertension, dyslipidemia and insulin resistance, features which often present in the CardioRenal metabolic syndrome. Here, we provide new insights in the pathogenesis of vascular stiffening induced by RAAS, including the dysfunction of vascular smooth muscle cells and endothelial cells; inflammation, oxidation stress, as well as alterations in collagen and elastin. We also introduce a novel concept where both β1-integrin and α-smooth muscle actin are likely major players in the increased vascular stiffening as ascertained by atomic force microscopy technology. We explore therapies such as estrogens aimed at vascular de-stiffening which may improve vascular function in patients. This review highlights recent evidence supporting the role of RAAS and insulin resistance in the development of vascular stiffening in diabetic patients.