Autonomic and endocrine participation in opioid peptide-induced hyperglycemia

Abstract Intracisternal administration of synthetic human β-endorphin to conscious, ambulatory adult male rats caused dose-related increases in plasma glucose concentration. The largest dose of β-endorphin examined, 7.25 nmol, increased plasma glucose concentration within 7 min and this effect lasted 2.5 h. On the other hand, only 58 pmol was required to induce transient hyperglycemia, when compared to the response observed in saline-injected control rats. This hyperglycemic effect of β-endorphin was prevented by prior systemic administration of naloxone, thus supporting the hypothesis that this β-endorphin-induced effect is mediated at opioid receptors. β-Endorphin also markedly increased plasma concentrations of epinephrine, norepinephrine and, to a lesser extent, dopamine. A significant positive correlation was demonstrated between plasma glucose and plasma epinephrine responses to increasing doses of intracisternally administered β-endorphin. In addition, intracisternal β-endorphin also increased plasma glucagon concentration without significantly increasing plasma insulin concentration. Thus, it is probable that epinephrine and glucagon are the major factors mediating this hyperglycemic effect. β-Endorphin-induced hyperglycemia was prevented by ganglionic blockade with chlorisondamine. This further supports the thesis that intracerebral β-endorphin increases plasma glucose concentration by activation of the central autonomic outflow. In addition to these effects on short-term regulators of glycemia, intracisternal β-endorphin increased plasma concentrations of corticosterone and growth hormone. Both of these glucose counterregulatory hormones may play minor roles in modulating β-endorphin-induced hyperglycemia.