Glucose modulation of islet monoamine oxidase activity in lean and obese hyperglycemic mice

Islet beta-cell monoamines are known to influence the insulin-releasing mechanisms. These amines are localized in the insulin-secretory granules and are inactivated by the enzyme monoamine oxidase (MAO), a hydrogen peroxide (H2O2)-generating enzyme. The activity of islet MAO may consequently be of importance for insulin secretion. In the present investigation, we studied the relation between islet MAO activity and plasma levels of insulin and glucose in obese (ob/ob) hyperglycemic mice and their lean littermates. In addition, the effect of glucose on the MAO activity of in vitro-cultured islets was studied. MAO activity was assayed with serotonin, dopamine (DA), and beta-phenylethylamine (PEA) as substrates. After an overnight fast in adult (age, 6 months) lean mice, islet MAO activity was increased by 35% to 70%. Plasma levels of glucose and insulin were markedly decreased as expected. However, fasting in adult obese mice either did not affect islet MAO activity (PEA and DA) or induced a slight decrease (serotonin) of approximately 25% (P < .05). Plasma glucose levels in adult obese mice were not significantly affected by the overnight fast. However, a correlation analysis based on individual adult obese mice (fed and fasted) showed a negative correlation between plasma glucose concentration and islet MAO activity with PEA (r = -.65, P < .02) and DA (r = -.66, P < .02), respectively. Further, a positive correlation (r = +.58, P < .05) was found between glucose level and islet MAO activity when using serotonin as substrate. There was no difference in islet MAO activity with PEA and DA as substrates in fed obese versus fed lean mice.(ABSTRACT TRUNCATED AT 250 WORDS)