The Role of Voltage-Gated Potassium Channels Kv2.1 and Kv2.2 in the Regulation of Insulin and Somatostatin Release from Pancreatic Isletss

The voltage-gated potassium channels Kv2.1 and Kv2.2 are highly expressed in pancreatic islets, yet their contribution to islet hormone secretion is not fully understood. Here we investigate the role of Kv2 channels in pancreatic islets using a combination of genetic and pharmacologic approaches. Pancreatic b-cells from Kv2.12/2 mice possess reduced Kv current and display greater glucose-stimulated insulin secretion (GSIS) relative to WT b-cells. Inhibition of Kv2.x channels with selective peptidyl [guangxitoxin-1E (GxTX-1E)] or small mole-cule (RY796) inhibitors enhances GSIS in isolated wild-type (WT) mouse and human islets, but not in islets from Kv2.12/2 mice. However, in WT mice neither inhibitor improved glucose tolerance in vivo. GxTX-1E and RY796 enhanced somatostatin release in isolated human and mouse islets and in situ perfuse