Decrease in catechol-O-methyltransferase activity in the liver of streptozotocin-induced diabetic rats.

摘要

1. The present study compared the activity of catechol- O-methyltransferase (COMT) in the liver and plasma of streptozotocin (STZ)-induced diabetic rats with that in normal rats. The activity of COMT was estimated by the metabolism of noradrenaline to metanephrine (MN), both measured by high-performance liquid chromatography with electrochemical detection. 2. Formation of MN was decreased in the liver of STZ- diabetic rats compared with normal rats. The amount of MN was also decreased in plasma obtained from STZ-diabetic rats. A Michaelis-Menten plot showed a reduction in the maximum velocity and an increase in the Km for COMT in liver samples from STZ-diabetic rats. 3. The role of hyperglycaemia in the lowering of COMT activity was then investigated using phlorizin or insulin at doses sufficient to normalize plasma glucose from STZ-diabetic rats. Both insulin and phlorizin treatment of STZ-diabetic rats for 4 days restored the activity of COMT to that seen in normal rats. Thus, correction of hyperglycaemia in STZ-diabetic rats can reverse the decrease in COMT activity. The activity of COMT is lower in STZ-diabetic rats than in normal rats mainly due to the higher plasma glucose.