Metabolic alterations induced by topical dimethylacetylenedicarboxylate

The disposition of topical dimethylacetylenedicarboxylate (DMAD) in tissue and its effect on glucose metabolism were studied in vivo, using skin grafted athymic nude mice, and in vitro, using excised pig skin. [14C]DMAD that penetrated skin grafts was distributed throughout the body. At 24 hr, the liver contained 15.62% of the applied dose. The kidneys, lungs, brain, and the heart contained 12.73, 5.61, 0.36, and 3.24% of the dose, respectively. One hour postapplication, DMAD markedly decreased [U-14C]glucose oxidation and the syntheses of fatty acids and glycogen in the livers and skin grafts. Similar effects were observed in excised pig skin. In addition, the activities of hepatic glucose-6-phosphate dehydrogenase, isocitric and NADP-malic dehydrogenase, and acetyl-CoA carboxylase were significantly reduced in DMAD-treated mice. In contrast, no effect was observed on the activity of glucokinase. The data indicate that DMAD rapidly penetrates the skin and causes aberrations in the activities of the glycogenic, lipogenic, and tricarboxylic acid metabolic pathways.