Reduction in Voltage-gated K+ Currents in Primary Cultured Rat Pancreatic Beta-cells by Linoleic Acids.
From: Prince Henry’s Institute of Medical Research, Clayton, Victoria, Australia. chen.chen@princehenrys.org
Endocrinology
- Publish Date: Feb 2006
- ISSN: 0013-7227
- Volume: 147
- Issue: 2
- Pages: 674-82
- Medium: Print
- Language: English
- Citation (JAMA): Feng Dan Dan, Luo Ziqiang, Roh Sang-Gun, et al. Reduction in Voltage-gated K+ Currents in Primary Cultured Rat Pancreatic Beta-cells by Linoleic Acids.. Endocrinology Feb 2006;147:674-82
Abstract
Free fatty acids (FFAs), in addition to glucose, have been shown to stimulate insulin release through the G protein-coupled receptor (GPCR)40 receptor in pancreatic beta-cells. Intracellular free calcium concentration ([Ca(2+)](i)) in beta-cells is elevated by FFAs, although the mechanism underlying the [Ca(2+)](i) increase is still unknown. In this study, we investigated the action of linoleic acid on voltage-gated K(+) currents. Nystatin-perforated recordings were performed on identified rat beta-cells. In the presence of nifedipine, tetrodotoxin, and tolbutamide, voltage-gated K(+) currents were observed. The transient current represents less than 5%, whereas the delayed rectifier current comprises more than 95%, of the total K(+) currents. A long-chain unsaturated FFA, linoleic acid (10 microm), reversibly decreased the amplitude of K(+) currents (to less than 10%). This reduction was abolished by the cAMP/protein kinase A system inhibitors H89 (1 microm) and Rp-cAMP (10 microm) but was not affected by protein kinase C inhibitor. In addition, forskolin and 8’-bromo-cAMP induced a similar reduction in the K(+) current as that evoked by linoleic acid. Insulin secretion and cAMP accumulation in beta-cells were also increased by linoleic acid. Methyl linoleate, which has a similar structure to linoleic acid but no binding affinity to GPR40, did not change K(+) currents. Treatment of cultured cells with GPR40-specific small interfering RNA significantly reduced the decrease in K(+) current induced by linoleic acid, whereas the cAMP-induced reduction of K(+) current was not affected. We conclude that linoleic acid reduces the voltage-gated K(+) current in rat beta-cells through GPR40 and the cAMP-protein kinase A system, leading to an increase in [Ca(2+)](i) and insulin secretion.
Mesh Headings (Keywords): Animals, Cells, Cultured, Cyclic AMP-Dependent Protein Kinases, Insulin, Insulin-Secreting Cells, Linoleic Acid, Male, Membrane Potentials, Potassium Channels, Voltage-Gated, RNA, Messenger, Rats, Rats, Sprague-Dawley, Rats, Wistar, Receptors, G-Protein-Coupled, Signal Transduction
Check for Full Text / PubMed Unique Identifier (PMID): 16254037
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