title: Linoleic acid stimulates [Ca2+]i increase in rat pancreatic beta-cells through both membrane receptor- and intracellular metabolite-mediated pathways.
abstract: The role of the free fatty acid (FFA) receptor and the intracellular metabolites of linoleic acid (LA) in LA-stimulated increase in cytosolic free calcium concentration ([Ca(2+)]i) was investigated. [Ca(2+)]i was measured using Fura-2 as indicator in rat pancreatic β-cells in primary culture. LA (20 µM for 2 min) stimulated a transient peak increase followed by a minor plateau increase in [Ca(2+)]i. Elongation of LA stimulation up to 10 min induced a strong and long-lasting elevation in [Ca(2+)]i. Activation of FFA receptors by the non-metabolic agonist GW9508 (40 µM for 10 min) resulted in an increase in [Ca(2+)]i similar to that of 2-min LA treatment. Inhibition of acyl-CoA synthetases by Triacsin C suppressed the strong and long-lasting increase in [Ca(2+)]i. The increase in [Ca(2+)]i induced by 2 min LA or GW9508 were fully eliminated by exhaustion of endoplasmic reticulum (ER) Ca(2+) stores or by inhibition of phospholipase C (PLC). Removal of extracellular Ca(2+) did not influence the transient peak increase in [Ca(2+)]i stimulated by 2 min LA or GW9508. The strong and long-lasting increase in [Ca(2+)]i induced by 10 min LA was only partially suppressed by extracellular Ca(2+) removal or thapsigargin pretreatment, whereas remaining elevation in [Ca(2+)]i was eliminated after exhaustion of mitochondrial Ca(2+) using triphenyltin. In conclusion, LA stimulates Ca(2+) release from ER through activation of the FFA receptor coupled to PLC and mobilizes mitochondrial Ca(2+) by intracellular metabolites in β-cells.
authors.affiliation: School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia. zhaoyf@fmmu.edu.cn
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Qiu
authors.forename: Dingjun
authors.initials: D
authors.lastname: Zha
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D019787:Linoleic Acid / Q000494:pharmacology*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D019284:Thapsigargin / Q000494:pharmacology; D014226:Triazenes / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D011956:Receptors, Cell Surface; D014226:Triazenes; D019284:Thapsigargin; C034613:triacsin C; D019787:Linoleic Acid; D010738:Type C Phospholipases; D002118:Calcium
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