Effects of an Enkephalin Analog on Pancreatic Endocrine Function and Glucose Homeostasis in Normal and Diabetic Dogs*

Abstract

The effects of an iv infusion of an enkephalin analog, [D-met2, Pro5]enkephalin-amide (enkephalin*), on circulating insulin, glucagon, and glucose concentrations were examined in vivo in normal and alloxan-diabetic dogs. Dose-response experiments in normal conscious dogs demonstrated inhibition of glucagon release (maximal decrease, 19 ± 10 pg/ml) at an infusion rate of 1.6 μg kg-1 h-1. At a dose of 32 μg kg-1 h-1, an increase of 44 ± 12 pg/ml in the glucagon concentration was observed. Both the degree of inhibition and stimulation of glucagon secretion were statistically significant compared to those seen after the infusion of enkephalin* together with naloxone. There was minimal suppression of insulin secretion at the lowest infusion dose, but significant stimulation (maximum increase, 5.0 ± 1.4 μ/ml) at the highest dose. This change was also prevented by naloxone. Similar effects were observed in the peripheral circulation of anesthetized dogs at an infusion rate of 32 μg kg-1 h-1. However, greater inc...