Endogenous opioid peptides stimulate post-exercise insulin response to glucose in rats

Exercise is associated with profound changes in glucose metabolism and insulin secretion. Endogenous opioid peptides may be involved in these metabolic adaptations. To gain insights into this hypothesis, we studied the effects of the opioid antagonist naloxone on the insulin response to glucose after a 2.5 h exercise bout, either by means of an intravascular glucose tolerance test in male Wistar rats or from rat islets of Langerhans isolated just after exercise. There was a tenfold increase in plasma beta-endorphin concentrations (9.8 +/- 2.1 vs. 114.2 +/- 22.0 fmol/ml, p < 0.001) in animals killed immediately after exercise. The in vivo post-exercise peak insulin response to glucose was markedly reduced compared to resting controls (p < 0.01). Interestingly, naloxone (10 mg/kg) still further decreased the insulin response compared to saline injected exercised rats (p < 0.05), but did not alter the response from resting animals. The post-exercise islet insulin response to 8.3 mM glucose was significantly reduced compared to resting rat islets (p < 0.05) and was further inhibited when naloxone (10 mu M) was added to the culture medium (p < 0.05). In another experiment, we also tested the effect of 10(-8) and 10(-6) M beta-endorphin on control islets. Both concentrations of beta-endorphin significantly increased the islet insulin response to 8.3 mM glucose (p < 0.05) and this effect was completely blocked by naloxone. These results suggest that endogenous opioid peptides participate in the physiological adaptation to exercise stress in maintaining post-exercise insulin response to glucose.