Insulin signaling in hypertension

Insulin resistance has been described in several diseases that increase cardiovascular risk and mortality, such as diabetes mellitus, obesity, essential hypertension, metabolic syndrome, and heart failure. In last years it has been clarified the role of insulin resistance in the pathogenesis of hypertension and target organ damage. Dysregulation of sympathetic nervous and renin–angiotensin systems resulting in enhanced stimulation of both adrenergic (ARs) and angiotensin II receptors (AT) are typical features of hypertension. Overactivity of the renin–angiotensin system observed in hypertension is likely to impair insulin signaling and contribute to insulin resistance. Actually, Ang II acting through the AT1 receptor inhibits the actions of insulin in vascular tissue, in part, by interfering with insulin signaling through PI3K and downstream Akt signaling pathways via generation of reactive oxygen species (ROS) by NADPH oxidase. On the contrary, stimulation of βARs is able to induce insulin resistance through the activation of different serine/threonine kinases that blunt the insulin signal by phosphorylating IR or IRS-1. Hypertension is also associated with an endothelial chronic inflammatory response characterized by altered cytokine production and activation of inflammatory signaling pathways, this activation results in an impairment of insulin signaling. Understanding the molecular mechanisms which can interfere with the impairment insulin signalling may be useful to improve blood pressure control as well as cardiac and cerebral protection in hypertension.