Role of arachidonate lipoxygenase and cyclooxygenase products in insulin and glucagon secretion from rat pancreatic islets.
Rat pancreatic islets incubated in nutrient medium were used to study the role of endogenous arachidonic acid metabolism in pancreatic hormone secretion. Both glucose and fetal calf serum stimulated radioimmunoassayable PGE2 production and insulin secretion from islets. These effects were abolished by the phospholipase inhibitor p-bromophenacyl bromide or by concurrent inhibition of cyclooxygenase and lipoxygenase by flurbiprofen plus nordihydroguaiaretic acid (NDGA), respectively. Bromophenacyl bromide also inhibited glucagon secretion. When used alone, flurbiprofen caused a significant enhancement of glucose-induced insulin secretion that was attributed to reactive stimulation of lipoxygenase-product formation rather than to selective cyclooxygenase inhibition. NDGA given alone in the presence of stimulatory concentrations of glucose suppressed the normal eight-fold rise in insulin secretion, but caused a marked enhancement in glucagon secretion that could be overcome by simultaneous inclusion of flurbiprofen. We concluded that: (1) Increased metabolism of arachidonic acid in pancreatic islets amplifies the secretion of insulin and glucagon. (2) The lipoxygenase as well as the cyclooxygenase pathways of arachidonate metabolism participate in the amplification of insulin secretion. (3) The observations made in this study are inconclusive with respect to the involvement of the lipoxygenase and cyclooxygenase pathways in glucagon secretion; an inhibitory role for lipoxygenase pathway products is suggested.
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001091:Arachidonate Lipoxygenases; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D001790:Blood Physiological Phenomena; D002396:Catechols / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D005480:Flurbiprofen / Q000494:pharmacology; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors; D008297:Male; D009637:Masoprocol; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats
D000098:Acetophenones; D001095:Arachidonic Acids; D002396:Catechols; D016861:Cyclooxygenase Inhibitors; D007328:Insulin; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D005480:Flurbiprofen; D009637:Masoprocol; D005934:Glucagon; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D005947:Glucose; C006821:4-bromophenacyl bromide