Abstract. The effect of human fl-endorphin (h(3E) infusion (0.2 mg/h) on glucose homeostasis was studied in 10 conscious overnight fasted dogs in which endocrine pancreatic function was fixed at basal levels with somatostatin plus intraportal replacement of basal insulin and glucagon.h#E caused a fall in plasma glucose from 107±5 to 76±6 mg/dl by 3 h (P < 0.01). This was due to a 25% fall in tracer-determined glucose production (Ra; P < 0.01). A significantly larger fall in Ra was observed in four dogs in which hypoglycemia was prevented by use of an exogenous glucose infusion (45 vs. 25%, P < 0.05). These changes occurred in the absence of changes in circulating levels of insulin, glucagon, epinephrine, norepinephrine, and cortisol.We conclude that the naturally occurring opioid peptide, f3-endorphin, inhibits glucose production by the liver in vivo. This appears to be a direct effect of the opioid on the liver, since the inhibition took place in the absence ofchanges in the other hormones measured. These results suggest that endorphins act on glucose homeostasis in a complex way, both by affecting other glucoregulatory hormones as demonstrated elsewhere, and by directly modulating hepatic glucose production as shown here.
IntroductionThe role of opioids in glucoregulation is not completely clear. Several reports (1-3) have shown that opioids can cause hy-