Kv2.1 ablation alters glucose-induced islet electrical activity, enhancing insulin secretion
- PMID: 17767909
- PMCID: PMC2699758
- DOI: 10.1016/j.cmet.2007.07.010
Kv2.1 ablation alters glucose-induced islet electrical activity, enhancing insulin secretion
Abstract
Voltage-gated potassium currents (Kv), primarily due to Kv2.1 channels, are activated by glucose-stimulated pancreatic beta cell depolarization, but the exact role (or roles) of this channel in regulating insulin secretion remains uncertain. Here we report that, compared with controls, Kv2.1 null mice have reduced fasting blood glucose levels and elevated serum insulin levels. Glucose tolerance is improved and insulin secretion is enhanced compared to control animals, with similar results in isolated islets in vitro. Isolated Kv2.1(-/-) beta cells have residual Kv currents, which are decreased by 83% at +50 mV compared with control cells. The glucose-induced action potential (AP) duration is increased while the firing frequency is diminished, similar to the effect of specific toxins on control cells but substantially different from the effect of the less specific blocker tetraethylammonium. These results reveal the specific role of Kv2.1 in modulating glucose-stimulated APs of beta cells, exposing additional important currents involved in regulating physiological insulin secretion.
Figures




References
-
- Ahn JE, Byun JH, Ko MS, Park SH, Lee MG. Case report: neuroendocrine carcinoma of the gallbladder causing hyperinsulinaemic hypoglycaemia. Clin Radiol. 2007;62:391–394. - PubMed
-
- Ashcroft FM, Rorsman P. Electrophysiology of the pancreatic beta-cell. Prog Biophys Mol Biol. 1989;54:87–143. - PubMed
-
- Beigelman PM, Thomas LJ, Shu MJ, Bessman SP. Insulin from individual isolated islets of Langerhans 2. Effect of glucose in varying concentrations. J Physiol (Paris) 1976;72:721–728. - PubMed
-
- Betsholtz C, Baumann A, Kenna S, Ashcroft FM, Ashcroft SJ, Berggren PO, Grupe A, Pongs O, Rorsman P, Sandblom J, et al. Expression of voltage-gated K+ channels in insulin-producing cells. Analysis by polymerase chain reaction. FEBS Lett. 1990;263:121–126. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Miscellaneous