Effects of naloxone on glucose homeostasis during insulin-induced hypoglycemia

The present study was designed to examine the role played by beta-endorphin in the physiological response to the stress of insulin-induced hypoglycemia. Three groups (n = 5, each) of conscious overnight-fasted dogs, chronically fitted with catheters in the femoral artery and in the third ventricle were used for these studies. Each experiment consisted of an 80-min equilibration period (0-80 min), a 40-min basal period (80-120 min), and a 180-min (120-300 min) experimental period. One group received a 220-min intracerebroventricular (icv) infusion of naloxone (0.2 mg/h) beginning at t = 80 min. The second group received a 3-h intravenous infusion of insulin at 5.0 mU.kg-1.min-1 beginning at t = 120 min. The third group received naloxone at t = 80 min and insulin beginning at t = 120 min, and both were continued throughout the experimental period. The studies show that insulin-induced hypoglycemia was associated with a rise in plasma cortisol, beta-endorphin, epinephrine, norepinephrine, and glucagon. Pretreatment with naloxone diminished the rises in plasma beta-endorphin, epinephrine, and norepinephrine without affecting the responses of plasma glucagon and cortisol. Although the levels of hypoglycemia achieved in the two groups were identical, glucose rates of appearance into and disappearance from the plasma compartment were higher in the group pretreated with icv naloxone (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)