OPIOID ANTAGONISM ALTERS BLOOD-GLUCOSE HOMEOSTASIS DURING EXERCISE IN HUMANS

In an attempt to clarify the role of endogenous opioid peptides in substrate mobilization and hormonal responses to dynamic exercise, eight trained cyclists completed exercise trials at 90% of maximal O-2 consumption (VO2 max ) until exhaustion and at 70% VO2 max for 90 min. Trials were conducted after intravenous administration of the opiate antagonist naloxone (NAL, 0.1 mg/kg bolus + 0.1 mg.kg(-1).h(-1)) or volume-matched saline (SAL) at each intensity. Serum glucose was maintained at significantly higher levels at 60 and 90 min of exercise in the 70%-NAL than in the 70%-SAL trial and at all points during exercise and at 30 and 60 min of recovery in the 90%-NAL than in the 90%-SAL trial. The serum insulin response to exercise was not altered by NAL administration at either intensity. Serum C-peptide was similar to 50% higher at 60 and 90 min of exercise in the 70%-NAL than in the 70%-SAL trial but was significantly lower during exercise in the 90%-NAL than in the 90%-SAL trial. The plasma glucagon response to exercise at 70% VO2 max was not altered by NAL administration but was significantly elevated in the 90%-NAL vs. the 90%-SAL trial. Plasma epinephrine was 50-150% (similar to 2-3 nM) higher during exercise from 30 to 90 min of exercise in the 70%-NAL than in the 70%-SAL trial and was higher at termination (4.9 +/- 2.1 vs. 2.7 +/- 1.7 nM) in the 90%-NAL than in the 90%-SAL trial, although the difference in the 90% trial was not statistically significant. Plasma norepinephrine was significantly higher at 10 min of exercise (19.1 +/- 2.8 vs. 11.6 +/- 1.7 nM) and at termination (21.0 +/- 1.7 vs. 12.2 +/- 1.4 nM) in the 90%-NAL than in the 90%-SAL trial but was unaltered in the 70%-NAL vs. the 70%-SAL trial. Thus, opiate antagonism prevents the decline in serum glucose and potentiates the epinephrine response during prolonged exercise while augmenting the hyperglycemic response to high-intensity exercise, presumably via elevations in plasma catecholamines and glucagon.