Beta endorphin modulation of the glucoregulatory effects of repeated epinephrine infusion in alloxan-diabetic and normal dogs

Abstract

When repeated epinephrine infusions are given to normal dogs as a partial stress model, there is exaggerated hyperglycaemia, associated with reduced plasma insulin levels and markedly decreased glucose clearance. In the present study, we have examined the hormonal and metabolic responses to two successive 60-min epinephrine (0.1 microgram . kg-1 . min-1) infusions with or without concomitant infusion of beta endorphin (0.3 microgram . kg-1 . min-1) in 6 alloxan-diabetic dogs. These studies have been compared to similar studies in 5 normal dogs. In the diabetic dogs, plasma glucose rose from 12.3 +/- 2.2 to 16.2 +/- 2.4 mmol/l (p less than 0.001) in response to the first epinephrine infusion and rose further to 18.1 +/- 2.5 mmol/l (p less than 0.001) during the second epinephrine infusion. The increases in plasma glucagon and glucose production were comparable with both infusions, but considerably greater than previously observed in normal dogs. In normal dogs, beta endorphin diminished the insulin response to the first epinephrine infusion (p less than 0.02), and abolished this response to the second (p less than 0.05). In addition beta endorphin also diminished the glucagon response to the second epinephrine infusion (p less than 0.01) and greatly potentiated epinephrine-induced suppression of glucose metabolic clearance during both infusions (p less than 0.001). However, beta endorphin did not appreciably alter the hyperglycaemic response to epinephrine due to a concomitant attenuation of the epinephrine-induced increase in hepatic glucose production. In contrast to normal dogs, beta endorphin did not modulate the effects of either the first or second epinephrine infusion on glucose kinetics in diabetic dogs. Also, beta endorphin failed to inhibit glucagon or insulin secretion in response to epinephrine in the diabetic animals. Since the alloxan-diabetic and normal dogs respond differently to the combined infusion of beta endorphin and epinephrine we conclude that the effects of beta endorphin observed in the normal dogs are dependent upon intact pancreatic endocrine function.