Kv1.3 potassium channel blockade as an approach to insulin resistance

Abstract

Diabetes mellitus is a devastating metabolic disease caused by either insulin deficiency or resistance and characterised by abnormal glucose, protein and lipid metabolism. It affects > 150 million people worldwide, 14 million in the US alone (90% Type II and 10% Type I) where it accounts for ∼ 15% of healthcare expenditure. Insulin resistance is a cardinal feature of Type II diabetes. The molecular mechanisms that mediate insulin resistance are under intense scrutiny, and a major goal of this effort is to uncover potential therapeutic targets. Recent data indicate that the voltage-gated potassium channel, Kv1.3, is an important regulator of peripheral insulin sensitivity and glucose metabolism. Indeed, Kv1.3 channel inhibition increases insulin sensitivity by decreasing inflammatory cytokines and by facilitating the translocation of GLUT4 to the plasma membrane. In light of these novel findings, the author believes that Kv1.3 is a promising target for the development of drugs useful in the management of insulin resistance and diabetes.