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¹ Department of Physiology, Xiangya Medical School, Central South University, Changsha, 410078 People's Republic of China² Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, Victoria 3168, Australia

(Correspondence should be addressed to C Chen; Email: chen.chen{at}princehenrys.org)

^* (D-D Feng and Y-F Zhao contributed equally to this work)

Free fatty acids (FFAs) regulate insulin secretion in a complex pattern and induce pancreatic β-cell dysfunction in type 2 diabetes. Voltage-dependent Ca²⁺ channels (VDCC) in β-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 β-cells. The VDCC current in primary cultured rat β-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 µM) significantly inhibited VDCC currents in β-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 β-cells nor did influence linoleic acid-induced inhibition of VDCC currents. Linoleic acid-induced inhibition of VDCC current was not blocked by preincubation of β-cells with either the specific protein kinase A (PKA) inhibitor, H89, or the PKC inhibitor, chelerythrine. However, pretreatment of β-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 β-cells via Ca²⁺-induced inactivation of VDCC.

This article has been cited by other articles:

				Y.-F. Zhao, J. Pei, and C. Chen Activation of ATP-sensitive potassium channels in rat pancreatic {beta}-cells by linoleic acid through both intracellular metabolites and membrane receptor signalling pathway J. Endocrinol., September 1, 2008; 198(3): 533 - 540. [Abstract] [Full Text] [PDF]