Journal of Research in Medical Sciences1735-19953169202609021176011760EN20260902The interplay between sympathetic nervous system activation and metabolic disorders, particularly type 2 diabetes mellitus (T2DM) and hypertension, has been increasingly recognized as a critical factor in cardiovascular morbidity and mortality. This review<br />explores the potential mechanisms linking sympathetic overactivity to insulin resistance (IR) and T2DM, highlighting the role of renal denervation (RDN) as a promising  therapeutic intervention. Sympathetic activation contributes to metabolic dysregulation<br />by increasing plasma fatty acids, enhancing hepatic gluconeogenesis, and impairing pancreatic insulin release, while also inducing vasoconstriction and reducing glucose uptake in skeletal muscle. RDN, a catheter?based procedure targeting renal sympathetic<br />nerves, has shown efficacy in managing resistant hypertension and improving glucose metabolism by reducing sympathetic drive, normalizing hepatic gluconeogenesis gene expression, and enhancing insulin sensitivity. Experimental and clinical studies suggest that RDN may mitigate IR, improve glycemic control, and reduce renal complications in diabetic models, independent of obesity or glucose tolerance status. However, the long?term effects on glycemic control and broader clinical applicability require further investigation.<br /><br />http://jrms.mui.ac.ir/index.php/jrms/article/view/11760http://jrms.mui.ac.ir/index.php/jrms/article/download/11760/6529