Adrenal demedullation blocks and brain norepinephrine depletion potentiates the hyperglycemic response to a variety of stressors

Abstract

The role of adrenal hormones in mediating the increase in blood glucose levels following several stressful stimuli (environmental and pharmacological) was studied. The role for brain norepinephrine systems in the initiation of the BG response to these challenges was investigated as well. There is disafreement as to whether stress-induced increases in blood glucose levels are mediated primarily by hormonal or neural stimulation of the liver. A stressful stimulus probably causes increases in blood glucose levels by activating neural connections from the brain to both the liver and the adrenal medulla. The relative contribution that each of these pathways makes to the overall blood glucose response may be dependent on certain factors, such as the type of preparation used (awake or anesthetized, fasted or fed) and the intensity of the stimulus used to induce hyperglycemia. In the experiments reported here, which were performed in awaka male rats, we found that increases in blood glucose levels following brief footshock stress, injection of 2-deoxy- d-glucose, exposure to the odor of a predator, and electrical stimulation of the hypothalamus were almost entirely eliminated by removal of the adrenal medullae, a procedure that does not damage hypothalamic norepinephrine systems or the multi-synaptic neural pathways from the hypothalamus to the liver. Furthermore, rather than having impaired blood glucose responses, rats that were depleted of brain norepinephrine showed normal responses to the injection of adrenergic agonists (including epinephrine), and potentiated responses to stressful stimuli compared to non-depleted controls. We conclude that: (1) rapid changes in blood glucose levels that occur following the stressful stimuli used here are mediated mainly by the release of epinephrine from the adrenal medullae and (2) intact brain norepinephrine systems are not required for these increases in blood glucose to occur.