Members of the Kv1 and Kv2 voltage-dependent K(+) channel families regulate insulin secretion
| Autor: | Xiao Fang Ha, Simon R. Smukler, Herbert Y. Gaisano, Patrick E. MacDonald, Jing Wang, Michael B. Wheeler, Peter H. Backx, Ann Marie F. Salapatek, Anthony M. Sun |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Potassium Channels
medicine.medical_treatment Gene Expression chemistry.chemical_compound Endocrinology Shab Potassium Channels 1-Methyl-3-isobutylxanthine Glyburide Insulin Secretion Insulin geography.geographical_feature_category Tetraethylammonium General Medicine Islet Recombinant Proteins Insulin oscillation Potassium Channels Voltage-Gated Kv1.4 Potassium Channel medicine.medical_specialty Protein subunit Genetic Vectors Green Fluorescent Proteins Biology Transfection Adenoviridae Cell Line Islets of Langerhans Internal medicine medicine Potassium Channel Blockers Repolarization Animals RNA Messenger Molecular Biology Insulinoma Messenger RNA geography Electric Conductivity medicine.disease Cyclic AMP-Dependent Protein Kinases Rats Pancreatic Neoplasms Luminescent Proteins Glucose chemistry Gene Deletion Delayed Rectifier Potassium Channels |
| Zdroj: | Molecular endocrinology (Baltimore, Md.). 15(8) |
| ISSN: | 0888-8809 |
| Popis: | In pancreatic β-cells, voltage-dependent K+ (Kv) channels are potential mediators of repolarization, closure of Ca2+ channels, and limitation of insulin secretion. The specific Kv channels expressed in β-cells and their contribution to the delayed rectifier current and regulation of insulin secretion in these cells are unclear. High-level protein expression and mRNA transcripts for Kv1.4, 1.6, and 2.1 were detected in rat islets and insulinoma cells. Inhibition of these channels with tetraethylammonium decreased IDR by approximately 85% and enhanced glucose-stimulated insulin secretion by 2- to 4-fold. Adenovirus-mediated expression of a C-terminal truncated Kv2.1 subunit, specifically eliminating Kv2 family currents, reduced delayed rectifier currents in these cells by 60–70% and enhanced glucose-stimulated insulin secretion from rat islets by 60%. Expression of a C-terminal truncated Kv1.4 subunit, abolishing Kv1 channel family currents, reduced delayed rectifier currents by approximately 25% and enhanced glucose-stimulated insulin secretion from rat islets by 40%. This study establishes that Kv2 and 1 channel homologs mediate the majority of repolarizing delayed rectifier current in rat β-cells and that antagonism of Kv2.1 may prove to be a novel glucose-dependent therapeutic treatment for type 2 diabetes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|