Increased SR phospholipid N-methylation in skeletal muscle of diabetic rats.
Phosphatidylethanolamine (PE) N-methylation was studied in skeletal muscle sarcoplasmic reticulum (SR) 6 wk after the induction of experimental diabetes in rats by an injection of streptozocin (65 mg/kg iv). A significant increase in the incorporation of radiolabeled methyl groups from S-adenosyl-L-methionine (AdoMet) into intramembranal PE was observed in diabetic preparations at 0.055 microM AdoMet, whereas the methylation activity was unaltered at 10 and 150 microM AdoMet concentrations. The increase in PE N-methylation activity was not evident until 28 days after streptozocin injection and was normalized by a 2-wk treatment of diabetic animals with insulin. In the presence of 10 microM of ATP and low concentrations of Ca2+ (0.1 microM), PE N-methylation was maximally activated, but the percent increase was similar in control, diabetes, and insulin-treated diabetes; at 100 microM Ca2+, however, N-methylation activity was depressed only in diabetic preparations. Calmodulin inhibitors such as compound 48/80 and calmidazolium (compound R24571) abolished the effect of Ca2+ and ATP on PE N-methylation in all three groups. Sarcolemmal (SL) PE N-methylation in diabetic skeletal muscle was also found to be increased at 0.055 microM AdoMet. The results suggest that intramembranal calmodulin may participate in regulating PE N-methylation in skeletal muscle membranes, but it may not be responsible for the high N-methylation activity in diabetic rats.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008745:Methylation; D008861:Microsomes / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012436:S-Adenosylmethionine / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D002147:Calmodulin; D010743:Phospholipids; D003189:p-Methoxy-N-methylphenethylamine; D004533:Egtazic Acid; D012436:S-Adenosylmethionine; D000255:Adenosine Triphosphate; D002118:Calcium