Effects of Insulin and Streptozotocin‐Induced Diabetes on Brain Norepinephrine Metabolism in Rats

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Abstract
Administration of insulin (2 IU/kg, i.p.) produced a significant decrease (18%) in forebrain norepinephrine and a significant increase in the major metabolite of norepinephrine, 3‐methoxy‐4‐hydroxyphenyl‐glycol‐sulfate (MOPEG‐SO4, +19%) in rats. Streptozotocin‐induced diabetes produced the opposite effects, resulting in an increase in forebrain norepinephrine (+17%) and a decrease in MOPEG‐SO4 (−26%). In addition, insulin increased (+143%) and diabetes decreased (− 41%) the turnover rate of norepinephrine, as measured by the rate of decrease of norepinephrine following inhibition of tyrosine hydroxylase by α‐methyl‐P‐tyrosine. All of these effects in diabetic rats were reversed by insulin replacement therapy. These data are discussed within the context of mood disorders characteristic of diabetic patients.