In:
Journal of Endocrinology, Bioscientifica, Vol. 196, No. 2 ( 2007-11-23), p. 377-384
Abstract:
Free fatty acids (FFAs) regulate insulin secretion in a complex pattern and induce pancreatic β-cell dysfunction in type 2 diabetes. Voltage-dependent Ca 2 + 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 Ca 2 + 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 Ca 2+ stores, completely abolished linoleic acid-induced decrease in VDCC current. Measurement of intracellular Ca 2+ concentration ([Ca 2+ ] i ) illustrated that linoleic acid induced an increase in [Ca 2+ ] i and that thapsigargin pretreatment inhibited this increase. Methyl-linoleic acid neither did induce increase in [Ca 2+ ] i nor did it block linoleic acid-induced increase in [Ca 2+ ] i . These results suggest that linoleic acid stimulates Ca 2+ release from intracellular Ca 2+ stores and inhibits VDCC currents in rat pancreatic β-cells via Ca 2+ -induced inactivation of VDCC.
Type of Medium:
Online Resource
ISSN:
0022-0795
,
1479-6805
Language:
Unknown
Publisher:
Bioscientifica
Publication Date:
2007
detail.hit.zdb_id:
1474892-7
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