New Insights into the Role of ENPP1 in Insulin Resistance

is a transmembrane glycoprotein highly expressed in adipocytes and also found in other tissues involved in glucose and lipid metabolism, including liver, skeletal muscle and beta cell of the pancreas. Early studies by Maddux and Goldfine [1] demonstrated that ENPP1 interacts with the insulin receptor at the level of the alpha subunit. This interaction results in decreased insulin-mediated activation of the tyrosine phosphorylation in the beta-subunit of the insulin receptor, and downstream insulin signaling activation. As a consequence, increased expression of ENPP1 in cell cultures has been shown to induce cellular insulin resistance [2]. The interest in this mechanism of cellular insulin resistance is accentuated by reports of an effect of ENPP1 gene variant on susceptibility to systemic insulin resistance, type 2 diabetes and cardiovascular disease [3]. Several investigators have pointed out that a common missense single nucleotide polymorphism of the ENPP1, the K121Q, associates wit