Phosphatidylethanolamine N-methylation and insulin release in isolated pancreatic islets of the rat.
Rat pancreatic islets methylate phosphatidylethanolamine (PE) lipids to form phosphatidylcholine (PC) with S-adenosyl-L-[methy-3H]methionine as the methyl donor. Islet PE-N-methyltransferase had activity optima at pH 6-7 and 8-9. S-Adenosyl-L-homocysteine, sodium deoxycholate, and Triton X-100 inhibited methylation in islet homogenates. Addition of phosphatidyl-N-monomethylethanolamine and phosphatidyl-N,N-dimethylethanolamine (PDME) enhanced [3H]methyl incorporation into PDME and PC, respectively. Isoproterenol, but not glucose, stimulated phospholipid methylation in islet homogenates. Propranolol inhibited the isoproterenol effect. In intact islets, glucose or isoproterenol stimulated insulin release and incorporation of [3H]methyl groups from [methyl-3H]methionine into phospholipids. Isoproterenol enhanced to a similar extent glucose-stimulated methylation and hormone release. Neither 2-deoxyglucose, tolbutamide, nor 8-bromo-cyclic AMP stimulated islet phospholipid methylation. The methyl-transferase inhibitor 3-deazaadenosine inhibited both glucose and isoproterenol-stimulated methyltransferase activity and insulin release. Propranolol inhibited the beta-adrenergic potentiation of glucose-induced phospholipid methylation and insulin release. These data suggest that PE-N-methyltransferase plays a role in amplification of the islet cell stimulus-secretion coupling response to certain secretagogues.
D000818:Animals; D005690:Galactose / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007536:Isomerism; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D050918:Phosphatidylethanolamine N-Methyltransferase; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D012435:S-Adenosylhomocysteine / Q000494:pharmacology; D014372:Tubercidin / Q000494:pharmacology
D007328:Insulin; C018258:3-deazaadenosine; D012435:S-Adenosylhomocysteine; D011433:Propranolol; D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase; D005947:Glucose; D007545:Isoproterenol; D014372:Tubercidin; D005690:Galactose