Hypothalamic noradrenergic and sympathoadrenal control of glycemia after stress.

Central noradrenergic pathways play a significant role in mediating blood glucose levels after neuroglycopenia. To further investigate hypothalamic noradrenergic neuronal activity (NNA) and sympathoadrenal influences in glucoregulation, we studied the effects of acute stress on glycemia and insulin release in normal and adrenalectomized (ADRX) rats. Within 5 min of exposure of rats to ether or cold-swim stress, significant positive correlations were evident between hypothalamic NNA and serum glucose levels (r = 0.70, P less than 0.001; at 15 min r = 0.78, P less than 0.0001). Five minutes after stress in the intact rat, insulin release was inhibited and serum insulin levels inversely correlated to hypothalamic NNA (r = 0.45, P less than 0.05). This relationship between insulin and NNA was no longer present 15 min after stress, but the levels of insulin remained inappropriately low with respect to the elevated serum glucose levels (approximately 30% above basal). Blockade of sympathetic noradrenergic pathways by treatment of intact rats with guanethidine prevented the rise in glucose after cold-swim stress but did not prevent the inhibition of insulin release. Fifteen minutes after exposure of ADRX rats to cold-swim stress their hypothalamic NNA and serum glucose levels were similar to intact animals. However, in contrast to their intact counterparts, serum insulin levels were significantly elevated (P less than 0.01). These data are consistent with central noradrenergic neural pathways directly mediating hepatic glucose release and indirectly inhibiting pancreatic insulin release via activation of adrenal medullary catecholamines.