Reduction in Voltage-Gated K+ Currents in Primary Cultured Rat Pancreatic ß-Cells by Linoleic Acids

Feng, Dan Dan, Luo, Ziqiang, Roh, Sang-gun, Hernandez, Maria, Tawadros, Neveen, Keating, Damien J and Chen ,Chen (2006) Reduction in Voltage-Gated K+ Currents in Primary Cultured Rat Pancreatic ß-Cells by Linoleic Acids. Erdocrinology, 147 2: 674-682. doi:10.1210/en.2005-0225

Author Feng, Dan Dan
Luo, Ziqiang
Roh, Sang-gun
Hernandez, Maria
Tawadros, Neveen
Keating, Damien J
Chen ,Chen
Title Reduction in Voltage-Gated K+ Currents in Primary Cultured Rat Pancreatic ß-Cells by Linoleic Acids
Journal name Erdocrinology   Check publisher's open access policy
ISSN 0013-7227
Publication date 2006-02
Year available 2006
Sub-type Article (original research)
DOI 10.1210/en.2005-0225
Volume 147
Issue 2
Start page 674
End page 682
Total pages 9
Place of publication Bethesda, MA
Publisher Endocrine Society
Collection year 2006
Language eng
Subject 110306 Endocrinology
110201 Cardiology (incl. Cardiovascular Diseases)
1201 Architecture
111201 Cancer Cell Biology
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 ß-cells. Intracellular free calcium concentration ([Ca2+]i) in ß-cells is elevated by FFAs, although the mechanism underlying the [Ca2+]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 ß-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 µM), 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 µM) and Rp-cAMP (10 µM) 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 ß-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 ß-cells through GPR40 and the cAMP-protein kinase A system, leading to an increase in [Ca2+]i and insulin secretion.
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Additional Notes With editorial comments as selected high impact paper in that issue (IF=5.313)

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