Phospholipase A2 activation may be a pivotal step in glucose-induced insulin secretion; however, recent studies have focused on only one by-product (arachi-donic acid). To examine the possible role of the other by-product (lysophospholipids), the lysoderivatives of alkylacyl-(ether linked) or diacylphospholipids were applied to rat islets in static incubations. 1-O-alkyl-2-lyso-sn-glyceryl-3-phosphorylcholine [lyso-PAF, the precursor of platelet-activating factor (PAF)] or lyso-phosphatidylcholine initiated insulin release at 1.7 mM glucose. Two preparations of PAF itself (0.005–5000 ng/ml) were without effect at 1.7 or 16.7 mM glucose, but PAF was nearly equipotent to lyso-PAF at >20 μg/ ml. A precursor-product relationship was suggested because the precursors (alkylacyl-or diacylglyceryl-phosphorylcholine) of all three active metabolites were inactive. The stimulatory effect of lyso-PAF is largely independent of any toxic or lytic effect, being biphasic, reversible, unassociated with impairment of the subsequent physiologic functioning of treated islets, and inhibitable (by Ni2+, La3+, or nordihydroguaiaretic acid but not by other lipoxygenase inhibitors). It also occurred at threshold concentrations at which islet morphology and 51Cr retention were preserved. Furthermore, lyso-PAF-induced insulin secretion was markedly impaired by reduced ambient temperature (16°C) or by the impermeant anion isethionate, further implying initiation of true exocytotic granule release and fission. Lyso-PAF (but not arachidonic acid) also circumvented the inhibition of glucose-induced insulin release caused by phospholipase inhibitors. Generation of endogenous lysophospholipids through exogenous application of phospholipase A2 also initiated insulin release, an effect responding to a panel of potential inhibitors identically to that induced by exogenously provided lysophospholipids. We propose that glucose activates phospholipase A2 in the pancreatic islet, leading to the generation of lysophospholipids; the latter may couple energy production to insulin release, at least in part via the promotion of Ca2+ translocation.
Ether-Linked Lysophospholipids Initiate Insulin Secretion: Lysophospholipids May Mediate Effects of Phospholipase A2 Activation on Hormone Release
Stewart A Metz; Ether-Linked Lysophospholipids Initiate Insulin Secretion: Lysophospholipids May Mediate Effects of Phospholipase A2 Activation on Hormone Release. Diabetes 1 July 1986; 35 (7): 808–817. https://doi.org/10.2337/diab.35.7.808
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