Phenylethanolamine N-methyltransferase in the brains of streptozotocin diabetic rats.

Recent evidence suggests that adrenergic neurons in the brainstem and hypothalamus are important for regulation of endocrine and cardiovascular function and the response to stress. Since abnormalities in several of these functions are observed in diabetic subjects, we investigated the effects of streptozotocin-induced diabetes on the activity of the enzyme that converts norepinephrine to epinephrine [phenylethanolamine N-methyltransferase (PNMT)] in the brainstem and hypothalamus of the rat. Enzyme activity was measured in the supernatant of sonicated brain tissues of saline-treated control, diabetic, and insulin-treated diabetic rats. One month after streptozotocin treatment, increases in plasma glucose and food intake occurred; these were restored to control levels by insulin treatment. PNMT activity was approximately 2-fold higher in the brainstem of diabetic rats than in controls (P less than 0.0001), and administration of insulin partially prevented the effects of diabetes on PNMT activity (P less than 0.01 compared to diabetics and P less than 0.05 compared to controls). Brainstem enzyme activity measured in all animals (n = 53) exhibited a significant correlation with plasma glucose concentrations (r = 0.51; P less than 0.001). Diabetes had no apparent effect on PNMT activity in the hypothalamus. These findings are the first to suggest that experimental diabetes alters PNMT activity in the medulla/pons.