Insulin Resistance and Endothelin: Another Pathway for Renal Injury in Patients With the Cardiometabolic Syndrome?

Abstract

Recent population studies suggest that insulin resistance and hyperinsulinemia, as well as the presence of the cardiometabolic syndrome, are associated with increased risk of chronic kidney disease. A considerable number of background studies support this association, proposing several mechanisms through which insulin resistance and hyperinsulinemia can harm the normal kidney. Current knowledge suggests that activation of the endothelin system can be an important factor contributing to the development of renal injury. Moreover, data from in vitro and in vivo studies have clearly shown that hyperinsulinemia stimulates the production and action of endothelin-1, an effect that is sustained in insulin-resistant states. Thus, insulin-mediated activation of the endothelin system can be another important pathway linking insulin resistance with kidney injury. This article discusses the existing data on the interactions between insulin resistance, hyperinsulinemia, and endothelin and how these can lead to renal damage in patients with the cardiometabolic syndrome.