Reduction in voltage-gated K+ currents in primary cultured rat pancreatic β-cells by linoleic acids

Dan Dan Feng, Ziqiang Luo, Sang Gun Roh, Maria Hernandez, Neveen Tawadros, Damien J. Keating, Chen Chen

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99 Citations (Scopus)

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 β-cells. Intracellular free calcium concentration ([Ca2+]i) in β-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 β-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 β-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 β-cells through GPR40 and the cAMP-protein kinase A system, leading to an increase in [Ca2+]i and insulin secretion.

Original languageEnglish
Pages (from-to)674-682
Number of pages9
JournalEndocrinology
Volume147
Issue number2
DOIs
Publication statusPublished - 2006 Feb

ASJC Scopus subject areas

  • Endocrinology

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