Lipoxygenation of arachidonic acid: a pivotal step in stimulus-secretion coupling in the pancreatic beta cell.

S. A. Metz, W. Y. Fujimoto, R. P. Robertson

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2141-2143
Number of pages3
JournalEndocrinology
Volume111
Issue number6
StatePublished - Dec 1982

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Insulin-Secreting Cells
Arachidonic Acid
Insulin
Lipoxygenase Inhibitors
Lipoxygenase
Calcium
Cyclic AMP
Prostaglandins
Phospholipids
4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine
Masoprocol
Sodium Salicylate
Tolbutamide
Endocrine Cells
Phospholipases
Theophylline
Ions
Glucose
Pharmaceutical Preparations

Cite this

Lipoxygenation of arachidonic acid : a pivotal step in stimulus-secretion coupling in the pancreatic beta cell. / Metz, S. A.; Fujimoto, W. Y.; Robertson, R. P.

In: Endocrinology, Vol. 111, No. 6, 12.1982, p. 2141-2143.

Research output: Contribution to journalArticle

Metz, SA, Fujimoto, WY & Robertson, RP 1982, 'Lipoxygenation of arachidonic acid: a pivotal step in stimulus-secretion coupling in the pancreatic beta cell.', Endocrinology, vol. 111, no. 6, pp. 2141-2143.
Metz, S. A. ; Fujimoto, W. Y. ; Robertson, R. P. / Lipoxygenation of arachidonic acid : a pivotal step in stimulus-secretion coupling in the pancreatic beta cell. In: Endocrinology. 1982 ; Vol. 111, No. 6. pp. 2141-2143.
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