Linoleic acid induces Ca2+-induced inactivation of voltage-dependent Ca2+ currents in rat pancreatic beta-cells.
Free fatty acids (FFAs) regulate insulin secretion in a complex pattern and induce pancreatic beta-cell dysfunction in type 2 diabetes. Voltage-dependent Ca2+ channels (VDCC) in beta-cells play a major role in regulating insulin secretion. The aim of present study is to clarify the action of the FFA, linoleic acid, on VDCC in beta-cells. The VDCC current in primary cultured rat beta-cells were recorded under nystatin-perforated whole-cell recording configuration. The VDCC was identified as high-voltage-gated Ca2+ channels due to there being no difference in current amplitude under holding potential between -70 and -40 mV. Linoleic acid (10 microM) significantly inhibited VDCC currents in beta-cells, an effect which was fully reversible upon washout. Methyl-linoleic acid, which does not activate G protein coupled receptor (GPR)40, neither did alter VDCC current in rat beta-cells nor did influence linoleic acid-induced inhibition of VDCC currents. Linoleic acid-induced inhibition of VDCC current was not blocked by preincubation of beta-cells with either the specific protein kinase A (PKA) inhibitor, H89, or the PKC inhibitor, chelerythrine. However, pretreatment of beta-cells with thapsigargin, which depletes intracellular Ca2+ stores, completely abolished linoleic acid-induced decrease in VDCC current. Measurement of intracellular Ca2+ concentration ([Ca2+](i)) illustrated that linoleic acid induced an increase in [Ca2+](i) and that thapsigargin pretreatment inhibited this increase. Methyl-linoleic acid neither did induce increase in [Ca2+](i) nor did it block linoleic acid-induced increase in [Ca2+](i). These results suggest that linoleic acid stimulates Ca2+ release from intracellular Ca2+ stores and inhibits VDCC currents in rat pancreatic beta-cells via Ca2+-induced inactivation of VDCC.[1]References
- Linoleic acid induces Ca2+-induced inactivation of voltage-dependent Ca2+ currents in rat pancreatic beta-cells. Feng, D.D., Zhao, Y.F., Luo, Z.Q., Keating, D.J., Chen, C. J. Endocrinol. (2008) [Pubmed]
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