Insulin rapidly increases diacylglycerol by activating de novo phosphatidic acid synthesis.
The mechanisms whereby insulin increases diacylglycerol in BC3H-1 myocytes were examined. When [3H]arachidonate labeling of phospholipids was used as an indicator of phospholipase C activation, transient increases in [3H]diacylglycerol were observed between 0.5 and 10 minutes after the onset of insulin treatment. With [3H]glycerol labeling as an indicator of de novo phospholipid synthesis, [3H]diacylglycerol was increased maximally at 1 minute and remained elevated for 20 minutes. [3H]Glycerol-labeled diacylglycerol was largely derived directly from phosphatidic acid. Insulin increased de novo phosphatidic acid synthesis within 5 to 10 seconds; within 1 minute, this synthesis was 60 times greater than that of controls. Thus, the initial increase in diacylglycerol is due to both increased hydrolysis of phospholipids and a burst of de novo phosphatidic acid synthesis. After 5 to 10 minutes, de novo phosphatidic acid synthesis continues as a major source of diacylglycerol. Both phospholipid effects of insulin seem important for generating diacylglycerol and other phospholipid-derived intracellular signaling substances.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002460:Cell Line; D004075:Diglycerides / Q000378:metabolism*; D004789:Enzyme Activation; D005989:Glycerides / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000096:biosynthesis*; D010716:Phosphatidylinositols / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D001095:Arachidonic Acids; D004075:Diglycerides; D005989:Glycerides; D007328:Insulin; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D010743:Phospholipids; D016718:Arachidonic Acid; D010738:Type C Phospholipases; D005990:Glycerol