Molecular Pharmacology, Vol 7, 465-479, Copyright © 1971 by the American Society for Pharmacology and Experimental Therapeutics

Effects of Menadione and Vitamin K₅ on Glucose Metabolism, Respiration, Lipolysis, Cyclic 3',5'-Adenylic Acid Accumulation, and Adenyl Cyclase in White Fat Cells

¹ Division of Biological and Medical Sciences, Brown University, Providence, Rhode Island 02912

The addition of menadione (2-methyl-l,4-naphthoquinone) to white fat cells in the presence of catecholamines and theophylline markedly increased the accumulation of cyclic AMP within 5 min. However, menadione inhibited the activation of adenyl cyclase by norepinephrine in fat cell "ghosts." Vitamin K₅ (2-methyl-4-amino-1-naphthol) actually inhibited cyclic AMP accumulation except under conditions in which autoxidation of K₅ occurred. The products obtained from air oxidation of vitamin K₅ were able to increase the cyclic AMP content of white fat cells in the presence of catecholamines and theophylline. The increase in cyclic AMP content due to menadione was largely intracellular and did not involve any alteration in the total ATP content of fat cells. Both menadione and vitamin K₅ (5 µg/ml) increased respiration, glucose oxidation, lactate accumulation, and fatty acid synthesis. The stimulation of respiration due to vitamin K₅ was potentiated by oligomycin, while that due to menadione was inhibited. The increases in oxygen consumption, lactate accumulation, glucose oxidation, and fatty acid biosynthesis produced by both menadione and vitamin K₅ were sensitive to cyanide. Antimycin A preferentially inhibited the increases in glucose metabolism and respiration due to menadione but had a smaller effect on those attributable to vitamin K₅. The insulin-like effects of these drugs could be distinguished from the action of insulin itself by the greater stimulation of fatty acid synthesis induced by insulin. Vitamin K₅, like insulin, inhibited the lipolytic action of catecholamines in the absence of theophylline after a lag period of 5 min, while in the presence of 1 mM theophylline the antilipolytic action was largely overcome. Insulin did not affect the accumulation of cyclic AMP, whereas vitamin K₅ reduced cyclic AMP accumulation under conditions in which these agents had equivalent effects on lipolysis. These results indicate that certain naphthoquinones can mimic the action of insulin on lipolysis and glucose metabolism while increasing cyclic AMP accumulation.

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ACKNOWLEDGMENTS The author is indebted to Dr. Judith Rosenthal for the ATP determinations, and Mrs. Anita Dodd for technical assistance.