TY - JOUR
T1 - Lipoxygenation of arachidonic acid
T2 - a pivotal step in stimulus-secretion coupling in the pancreatic beta cell.
AU - Metz, S. A.
AU - Fujimoto, W. Y.
AU - Robertson, R. P.
PY - 1982/12
Y1 - 1982/12
N2 - The relationship(s) between calcium flux, phospholipid turnover and stimulus-secretion coupling in endocrine cells remains unclear. Several stimuli of insulin secretion promote calcium accumulation in the pancreatic beta cell; recent studies are compatible with the formulation that, as a consequence of such ion flux, arachidonic acid is released from phospholipids by calcium-dependent phospholipase(s), and may, in turn, be metabolized via lipoxygenase to products which promote insulin release. In the current study, we examined the effects of two known lipoxygenase inhibitors, BW755c and nordihydroguaiaretic acid, on the augmentation of insulin release evoked by three pharmacologically distinct classes of insulin secretagogues--one which augments cyclic AMP accumulation (exemplified by theophylline), one which inhibits prostaglandin synthesis (sodium salicylate), and one which is independent of changes in cyclic AMP or prostaglandin availability (tolbutamide). Both inhibitors of lipoxygenase markedly blunted the insulinogenic response to glucose, as well as to all three drugs, without evidence of cell toxicity. These data are most compatible with a central role for lipoxygenase products in coupling insulin secretion to stimuli of widely varying natures.
AB - The relationship(s) between calcium flux, phospholipid turnover and stimulus-secretion coupling in endocrine cells remains unclear. Several stimuli of insulin secretion promote calcium accumulation in the pancreatic beta cell; recent studies are compatible with the formulation that, as a consequence of such ion flux, arachidonic acid is released from phospholipids by calcium-dependent phospholipase(s), and may, in turn, be metabolized via lipoxygenase to products which promote insulin release. In the current study, we examined the effects of two known lipoxygenase inhibitors, BW755c and nordihydroguaiaretic acid, on the augmentation of insulin release evoked by three pharmacologically distinct classes of insulin secretagogues--one which augments cyclic AMP accumulation (exemplified by theophylline), one which inhibits prostaglandin synthesis (sodium salicylate), and one which is independent of changes in cyclic AMP or prostaglandin availability (tolbutamide). Both inhibitors of lipoxygenase markedly blunted the insulinogenic response to glucose, as well as to all three drugs, without evidence of cell toxicity. These data are most compatible with a central role for lipoxygenase products in coupling insulin secretion to stimuli of widely varying natures.
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M3 - Article
C2 - 6814899
AN - SCOPUS:0020453646
VL - 111
SP - 2141
EP - 2143
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 6
ER -