Redox Functions of Heme Oxygenase-1 and Biliverdin Reductase in Diabetes

In patients with diabetes, the hyperglycemia-driven excess generation of reactive oxygen species (ROS) induces oxidative stress (OS) in a variety of tissues. OS is closely associated with chronic inflammation and has a key role in the pathogenesis of vascular complications. The enzymes that generate ROS and gasotransmitters are redox regulated and are implicated in cellular signaling. As a result of cellular metabolism, cells produce significant amounts of carbon monoxide (CO), mainly from heme degradation catalyzed by heme oxygenases (HOs). These reactions also generate biliverdin, bilirubin (BR), and iron. The conversion of biliverdin to BR is catalyzed by biliverdin reductase-A (BVR-A). In this review, we focus on the importance of the HO-1/CO system and BVR in the pathophysiology and therapy of inflammation associated with diabetes.