Exploring the mechanisms connecting the sympathetic nervous system and type 2 diabetes: Focus on renal denervation

Abstract

The 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 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 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 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.