INFLUENCE OF BETA-2-ADRENOCEPTOR STIMULATION AND GLUCOSE ON ISLET MONOAMINE-OXIDASE ACTIVITY AND INSULIN SECRETORY RESPONSE IN THE MOUSE

Changes in the content of monoamines such as dopamine (DA) and seroton in (5-HT) in the insulin granules are known to influence insulin relea se. The monoamines are inactivated by monoamine oxidase (MAO), a hydro gen peroxide-generating enzyme, which may be of importance for the red ox state of the beta-cell. We studied the action of two different insu lin secretagogues, the beta2-adrenoceptor agonist terbutaline and gluc ose, on islet MAO activity and the plasma levels of insulin and glucos e. MAO was assayed with 5-HT, DA, and beta-phenylethylamine as substra tes. At 6 min (but not at 2 or 30 min) after terbutaline injection, ma rked increases of islet MAO activity and the plasma insulin levels wer e recorded. The plasma glucose levels were of the same magnitude at al l time points. Injection of glucose moderately suppressed enzyme activ ity at 2 min. This occurred concomitantly with the peak increase in pl asma levels of insulin and glucose. At 60 min, when the plasma levels of glucose and insulin were restored to basal, a slight increase in MA O activity was observed. At 2 min after injection of different doses o f glucose mixed with a maximal dose of terbutaline, the insulin secret ory response was either increased (submaximal glucose dose) or unaffec ted (maximal dose of glucose) by the beta2-adrenoceptor stimulator. Ho wever, when a maximal dose of glucose was given at 6 min after terbuta line, i.e., when islet MAO activity was increased, the insulin respons e to glucose was suppressed. Starvation for 24 h induced an increase i n islet MAO activity. Moreover, this fasting period suppressed the glu cose-induced insulin response, whereas insulin release induced by beta 2-adrenoceptor stimulation was unaffected. The results suggest that bo th glucose and terbutaline influence insulin secretion through their a ction on islet MAO. Glucose inhibits and terbutaline increases the enz yme activity. In addition to reducing the islet monoamine content, an increased MAO activity also generates hydrogen peroxide, which might n egatively modulate the insulin release induced by secretagogues that d epend on a reductive redox state of the beta-cell (thiol dependent; e. g., glucose) and facilitate the release by non-thiol-dependent (e.g., terbutaline) secretagogues.