Insulin-stimulated hydrolysis of a novel glycolipid generates modulators of cAMP phosphodiesterase.
Insulin action may involve the intracellular generation of low molecular weight substances that modulate certain key enzymes. The production of two substances that regulate the activity of adenosine 3',5'-monophosphate phosphodiesterase was evaluated in cultured myocytes by incorporation of radiolabeled precursors. Insulin caused the rapid hydrolysis of a chemically undefined membrane glycolipid, resulting in the production of two related complex carbohydrates as well as diacylglycerol. Both the glycolipid precursor and the aqueous products were monitored by labeling with radioactive inositol and glucosamine. Depletion of the labeled precursor and the appearance of labeled water-soluble products and diacylglycerol occurred within 30 seconds after hormone treatment and was followed by rapid resynthesis of the precursor. The aqueous products that were radioactively labeled appeared chromatographically and electrophoretically identical to phosphodiesterase modulating activities produced by insulin from the same cells. The purified radiolabeled and bioactive substances had similar chemical properties. Hydrolysis of the glycolipid precursor and subsequent generation of products could be reproduced by incubation of extracted lipids with a phosphatidylinositol-specific phospholipase C. These studies suggest that insulin stimulates an endogenous, selective phospholipase C activity that hydrolyzes a novel glycolipid, resulting in the generation of a complex carbohydrate-phosphate substance containing inositol and glucosamine that may mediate some of the actions of the hormone.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D005944:Glucosamine / Q000378:metabolism; D006017:Glycolipids / Q000378:metabolism*; D006868:Hydrolysis; D007294:Inositol / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D051379:Mice; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D013211:Staphylococcus aureus / Q000201:enzymology
D006017:Glycolipids; D007328:Insulin; D007294:Inositol; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D005944:Glucosamine