Insulin Rapidly Increases Diacylglycerol by Activating De Novo Phosphatidic Acid Synthesis

• Published in: Science (American Association for the Advancement of Science) Vol. 236; no. 4801; pp. 586 - 589
• Main Authors: Farese, Robert V., Konda, Thomas Suman, Davis, John S., Standaert, Mary L., Pollet, Robert J., Cooper, Denise R.
• Format: Journal Article
• Language: English
• Published: Washington, DC The American Association for the Advancement of Science 01.05.1987; American Association for the Advancement of Science
• Subjects: Acids; Arachidonic Acid; Arachidonic Acids - metabolism; Biochemistry; Biological and medical sciences; Cell Line; Cell physiology; diacylglycerol; Diglycerides; Diglycerides - metabolism; Enzyme Activation; Enzymes; Fundamental and applied biological sciences. Psychology; Glycerides - metabolism; Glycerol - metabolism; Hormonal regulation; Hydrolysis; Insulin; Insulin - pharmacology; Kinetics; Lipids; Memory interference; Molecular and cellular biology; Muscle cells; Muscles - drug effects; Muscles - metabolism; myocytes; Phosphatidic acids; Phosphatidic Acids - biosynthesis; Phosphatidylinositols - metabolism; phospholipase C; Phospholipids; Phospholipids - metabolism; Physiological aspects; Polysaccharides; Proton pump inhibitors; Radioactive decay; Type C Phospholipases - metabolism; Cell culture; Protein hormone; Diglyceride; Transduction signal; Phospholipid; Activation; Biosynthesis; Insulin; Phosphatidic acid; Myocyte
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.3107122

The mechanisms whereby insulin increases diacylglycerol in BC3H-1 myocytes were examined. When [$^{3}$H]arachidonate labeling of phospholipids was used as an indicator of phospholipase C activation, transient increases in [$^{3}$H]diacylglycerol were observed between 0.5 and 10 minutes after the onset of insulin treatment. With [$^{3}$H]glycerol labeling as an indicator of de novo phospholipid synthesis, [$^{3}$H]diacylglycerol was increased maximally at 1 minute and remained elevated for 20 minutes. [$^{3}$H]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.