Activation of the sympathetic nervous system precedes activation of the parasympathetic nervous system during hypoglycemia

It has been proposed that during hypoglycemia the parasympathetic nervous system is activated before the sympathetic nervous system, and that parasympathetic activation is an all or none phenomenon. To test these hypotheses, we assessed plasma epinephrine and norepinephrine responses, indices of sympathetic activation, and plasma pancreatic polypeptide responses, an index of parasympathetic, activation, during stepwise hypoglycemic clamp studies in 14 normal volunteers. Plasma epinephrine and norepinephrine concentrations increased significantly during the first glycemic plateau (4.4 mM) from 0.31±0.03 to 0.63±0.07 pmol/l and from 1.25±0.05 to 1.47±0.06 nmol/l respectively, both p<0.02, whereas plasma pancreatic polypeptide concentrations remained unchanged (16±3 vs 19±4 pmol/l, p>0.5), but increased at the next glycemic plateau (3.7 mM) to 37±8 pmol/l, p<0.02. A further decrease in plasma glucose concentration increased pancreatic polypeptide concentrations further to 65±11 pmol/l, p<0.03. We, therefore, conclude that during hypoglycemia sympathetic nervous system activation precedes that of the parasympathetic nervous system and that the latter is not an all or nothing phenomenon.