Pancreatic islet arachidonic acid turnover and metabolism and insulin release in response to delta-9-tetrahydrocannabinol.
Isolated pancreatic islets from the rat secrete insulin in response to glucose or delta-9-tetrahydrocannabinol (THC). THC stimulated the basal release of insulin and also potentiated the secretory response to glucose. The exposure of control or glucose-stimulated islets to THC inhibited the incorporation of [14C]arachidonic acid (AA) into phospholipids. However, in islets prelabeled with [14C]AA, THC enhanced the glucose-induced loss of AA from phospholipids. The enhanced AA release from islet phospholipids in response to glucose and THC was accompanied by increased synthesis of 12-L-[5,6,8,9,11,12,14,15-3H(N)]-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) and prostaglandin E2. The lipoxygenase inhibitor 3-amino-1-(3-trifluoromethylphenyl)-2-pyrazoline hydrochloride (BW755C) inhibited 12-HETE synthesis and insulin release in glucose and THC-challenged islets; nordihydroguaiaretic acid also inhibited insulin release in THC-treated islets. In contrast, the cyclooxygenase inhibitor, indomethacin, stimulated insulin release. In homogenized islet preparations, THC inhibited acyl-CoA acyltransferase, while it stimulated phospholipase A2 activity. The stimulatory effects of THC on islet cell AA hydrolysis from phospholipids, lipoxygenase product formation, and secretion suggests that these biochemical sequelae in cell activation are important modulators of insulin release.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002250:Carbon Radioisotopes; D013759:Dronabinol / Q000494:pharmacology*; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D051381:Rats
D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D006893:Hydroxyeicosatetraenoic Acids; D007328:Insulin; D010743:Phospholipids; D016718:Arachidonic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D013759:Dronabinol