Dual action of antidepressant drugs (MAO inhibitors) on insulin release.

Experiments have been carried out to investigate the role of monoamine oxidase (MAO) in the mechanism of insulin release. Isolated islets and pieces of rat pancreas were incubated in media of high glucose content in the presence of various concentrations of MAO inhibitors. At the end of the incubation, the islet MAO activity and the concentration of insulin released into the medium was measured. The results have shown that: 1. Glucose-mediated insulin release was potentiated by low concentrations of MAO inhibitors, the highest effect being observed at 10 muM. 2. Islet MAO activity was completely abolished in the presence of 10 muM of MAO inhibitors, while at lower concentrations, partial inhibition of enzyme could be achieved. A rise in the concentration of MAO inhibitors was accompanied by a decline in their potentiating effect on insulin secretion. No potentiation was observed at 1 mM concentration, and total inhibition of glucose-mediated insulin release was obtained in the presence of 5-10 mM of MA9 inhibitors. The potentiation of insulin release caused by two of the MAO inhibitors studied was abolished by addition of 1 muM epinephrine into the incubation medium. The basal rate of insulin release was insensitive to low concentrations of MAO inhibitors, but an inhibitory effect was obtained when concentrations were raised to 10 mM. In a comparative study, it was found that MAO activity was greater in liver than in islet tissue, while islets contained three times the activity of exocrine pancreas, consistent with previous findings in islet-cell tumors. The data presented here clearly show that MAO inhibitors are capable of both potentiating and inhibiting insulin release in vitro, depending on their concentrations. It is concluded that the stimulation of glucose-mediated insulin secretion may be related to the MAO inhibitory effects of the drugs, while the inhibition observed at concentrations greater than 1 times 10-3M is due to some other unidentified mechanism.