Influence of beta 2-adrenoceptor stimulation and glucose on islet monoamine oxidase activity and insulin secretory response in the mouse

Abstract

Changes in the content of monoamines such as dopamine (DA) and serotonin (5-HT) in the insulin granules are known to influence insulin release. The monoamines are inactivated by monoamine oxidase (MAO), a hydrogen peroxide-generating enzyme, which may be of importance for the redox state of the beta-cell. We studied the action of two different insulin secretagogues, the beta 2-adrenoceptor agonist terbutaline and glucose, on islet MAO activity and the plasma levels of insulin and glucose. MAO was assayed with 5-HT, DA, and beta-phenylethylamine as substrates. At 6 min (but not at 2 or 30 min) after terbutaline injection, marked increases of islet MAO activity and the plasma insulin levels were recorded. The plasma glucose levels were of the same magnitude at all time points. Injection of glucose moderately suppressed enzyme activity at 2 min. This occurred concomitantly with the peak increase in plasma levels of insulin and glucose. At 60 min, when the plasma levels of glucose and insulin were restored to basal, a slight increase in MAO activity was observed. At 2 min after injection of different doses of glucose mixed with a maximal dose of terbutaline, the insulin secretory response was either increased (submaximal glucose dose) or unaffected (maximal dose of glucose) by the beta 2-adrenoceptor stimulator. However, when a maximal dose of glucose was given at 6 min after terbutaline, i.e., when islet MAO activity was increased, the insulin response to glucose was suppressed. Starvation for 24 h induced an increase in islet MAO activity.(ABSTRACT TRUNCATED AT 250 WORDS)