Comparison of glucagon responses to 2-deoxy-D-glucose and hypoglycemia in man

2-Deoxy-D-glucose (2DG), by competitive inhibition of glucose utilization, produces a state of intracellular glucopenia with resultant activation of both the sympathetic and parasympathetic branches of the autonomic nervous system. We have investigated the relationship between the activation of the autonomic nervous system caused by this drug and glucagon secretion. Subjects experienced symptoms identical to those observed during true hypoglycemia and demonstrated a marked rise in both gastric acid secretion and urinary epinephrine excretion. Mean immunoreactive glucagon (IRG) levels rose only slightly post-2DG (maximal mean increment, 18 pg/ml). Insulin-induced hypoglycemia, although eliciting a similar increase in urinary epinephrine excretion, was followed by a severalfold increase in IRG. Thus, although hypoglycemia and 2DG induced similar discharge of the autonomic nervous system, the glucagon response to hypoglycemia was much greater. These observations provide strong evidence that marked increases in sympathetic and parasympathetic discharge in man are weak alpha-cell stimuli and further support the hypothesis that the rise in IRG that occurs during hypoglycemia is not mediated primarily via the autonomic nervous system.