| First Author | Li XN | Year | 2013 |
| Journal | J Pharmacol Exp Ther | Volume | 344 |
| Issue | 2 | Pages | 407-16 |
| PubMed ID | 23161216 | Mgi Jnum | J:244135 |
| Mgi Id | MGI:5912914 | Doi | 10.1124/jpet.112.199083 |
| Citation | Li XN, et al. (2013) The role of voltage-gated potassium channels Kv2.1 and Kv2.2 in the regulation of insulin and somatostatin release from pancreatic islets. J Pharmacol Exp Ther 344(2):407-16 |
| abstractText | 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 beta-cells from Kv2.1(-/-) mice possess reduced Kv current and display greater glucose-stimulated insulin secretion (GSIS) relative to WT beta-cells. Inhibition of Kv2.x channels with selective peptidyl [guangxitoxin-1E (GxTX-1E)] or small molecule (RY796) inhibitors enhances GSIS in isolated wild-type (WT) mouse and human islets, but not in islets from Kv2.1(-/-) 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 perfused pancreata from WT and Kv2.1(-/-) mice. Kv2.2 silencing in mouse islets by adenovirus-small hairpin RNA (shRNA) specifically enhanced islet somatostatin, but not insulin, secretion. In mice lacking somatostatin receptor 5, GxTX-1E stimulated insulin secretion and improved glucose tolerance. Collectively, these data show that Kv2.1 regulates insulin secretion in beta-cells and Kv2.2 modulates somatostatin release in delta-cells. Development of selective Kv2.1 inhibitors without cross inhibition of Kv2.2 may provide new avenues to promote GSIS for the treatment of type 2 diabetes. |
