Circulating dopamine-beta-hydroxylase in the rat: importance of altered disposal pathways in experimental diabetes

Circulatory dopamine-beta-hydroxylase (DBH) activity was increased as much as 6-fold in rats with streptozotocin-induced diabetes mellitus. The increased enzymatic activity correlated with increased DBH protein as assessed by neutralization with homologous antiserum. The high levels of circulating DBH activity induced by streptozotocin was associated with a markedly slowed disappearance of enzyme activity after the i.v. injection of exogenous bovine DBH or exogenous rat DBH. Treatment of streptozotocin-treated rats with insulin prevented the increase in circulating DBH activity and reduced the initial half-time of disappearance of bovine DBH in a dose-related manner; the correlation between the initial half-time of disappearance of the bovine enzyme and the circulating DBH activity level was strongly positive. These results indicate that a reduction in the metabolic clearance rate of circulating DBH is a major factor accounting for the increase in serum DBH activity in the streptozotocin-diabetic rat.