Glucoprivation by insulin leads to trans-synaptic increase in rat adrenal tyrosine hydroxylase mRNA levels

Effects of single or repeated insulin or 2-deoxy-D-glucose administration on adrenal tyrosine hydroxylase mRNA and protein levels were examined in rats. Insulin produced hypoglycemia and an elevation in plasma epinephrine and norepinephrine levels. A significant increase (3-5-fold) 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 consecutive injection of insulin or 2-deoxy-D-glucose. Whereas insulin treatment raised tyrosine hydroxylase mRNA levels in intact adrenals, no increase in tyrosine hydroxylase mRNA levels occurred following adrenal denervation by splanchnic nerve transection. Western blot analysis showed that although a single insulin treatment did not affect tyrosine hydroxylase protein levels, a significant increase was observed following 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 nerve.