GLUCOPRIVATION BY INSULIN LEADS TO TRANSSYNAPTIC INCREASE IN RAT ADRENAL TYROSINE-HYDROXYLASE MESSENGER-RNA LEVELS

Effects of single or repeated insulin or 2-deoxy-D-glucose administrat ion on adrenal tyrosine hydroxylase mRNA and protein levels were exami ned in rats. Insulin produced hypoglycemia and an elevation in plasma epinephrine and norepinephrine levels. A significant increase (3-5-fol d) in tyrosine hydroxylase mRNA levels was found at 5 h, decreasing to near basal levels at 24 h following the first and also the sixth cons ecutive injection of insulin or 2-deoxy-D-glucose. Whereas insulin tre atment raised tyrosine hydroxylase mRNA levels in intact adrenals, no increase in tyrosine hydroxylase mRNA levels occurred following adrena l denervation by splanchnic nerve transection. Western blot analysis s howed that although a single insulin treatment did not affect tyrosine hydroxylase protein levels, a significant increase was observed follo wing the seventh administration. This study shows that insulin-induced hypoglycemia increases tyrosine hydroxylase gene expression and that this process is regulated by a central mechanism via the splanchnic ne rve.