Potassium channel-targeted therapy in reducing vascular complications in diabetes mellitus: novel insights

Potassium (K⁺) channels are the most diverse group of ion channels and are required for many physiological functions such as cell excitability and insulin secretion. They are widely distributed throughout the body, but the majority of their subclasses are found in blood vessels, more specifically in the vascular smooth muscle cells (VSMCs) and in the endothelial cells (ECs). In blood vessels, they participate in the regulation of proper vascular tone. Certain diseases may impair the structure and function of vascular K⁺ channels and decrease their expression in the blood vessels, causing improper blood flow through vital organs and vascular tone dysfunction. These changes lead to clinically significant diseases (hypotension, hypertension, atherosclerosis, cerebrovascular diseases, etc.), which increase total and cardiovascular mortality. Diabetes mellitus (DM) is a condition that significantly alters the structure and function of K⁺ channels in the blood vessels. These changes contribute to the development of common DM-associated chronic macrovascular and microvascular complications, which further increases morbidity and mortality. These complications are especially prominent in diabetes mellitus type 2 (T2DM). Moreover, other concomitant pathophysiological processes impair K⁺ channels, which accelerate the progression of DM. This profound bidirectional patophysiological connection between DM and vascular K⁺ channels may redirect future antidiabetic therapy to novel mechanisms that include modulation of these channels. This up-to-date review summarizes the contribution of DM-induced vascular K⁺ channel dysfunction to vascular complications of DM and future directions in the development of novel K⁺ channels-targeted therapy for vascular disorders.