Effects of dimethylsulfoxide on cyclic AMP accumulation, lipolysis and glucose metabolism of fat cells

Dimethylsulfoxide (DMSO) decreased insulin-stimulated [l-¹⁴C]glucose oxidation and increased lipolysis. DMSO also potentiated the rise in lipolysis due to glucagon, norepinephrine or theophylline. The rise in cyclic AMP levels due to these lipolytic agents was increased by 1.10 M DMSO. This erfect was rapid in onset, since increases in cyclic AMP due to DMSO were detected as early as 40 sec after addition of lipolytic agents. The drop in cyclic AMP accumulation seen after addition of propranolol to fat cells incubated with norepinephrine was reduced by DMSO. DMSO inhibited both the soluble and particulatc cyclic AMP phosphodiesterase activity present in fat cells. The metabolites of DMSO. dimethylsulfonc and dimethylsulfide. did not cause any change in cyclic AMP accumulation due to norepinephrine. indicating that DMSO and not a metabolite was responsible for the observed effects. These data indicate that DMSO at high concentrations inhibited cyclic AMP phosphodiesterase and is a stimulator of cyclic AMP accumulation and lipolysis in fat cells.