Beta-endorphin inhibits insulin secretion from isolated pancreatic islets

Abstract

Intravenous administration of small doses of beta-endorphin causes immediate suppression of basal and glucose-stimulated insulin secretion in normal rabbits. The purpose of the present study was to determine if beta-endorphin directly inhibits glucose-stimulated insulin secretion from rabbit pancreatic islets. Islets were isolated from male New Zealand White rabbits and perifused for 1 h with medium containing 100 mg/dl glucose (M100) followed by a 1-h challenge with medium containing 300 mg/dl glucose (M300) with or without beta-endorphin and/or the specific opioid antagonist naloxone. Samples were collected every 5 min during the last 30 min of the baseline perifusion with M100 and during the 1-h challenge with the stimulatory concentration of glucose (M300). Total insulin secretion for each 1-h period was calculated by adding the areas under the curves for twice the 30-min baseline period and for the 1-h challenge period. The mean +/- SE area for the control islets during perifusion with M100 was 5.9 +/- 0.8 microU/islet.h. M300 stimulated a 4.2-fold increase in the amount of insulin secreted (24.5 +/- 3.6 microU/islet.h). The stimulated rate of insulin release was sustained throughout the 1-h test period with M300, averaging 0.42 +/- 0.02 microU insulin/islet.min. beta-Endorphin inhibited glucose-stimulated insulin secretion in a concentration-dependent manner. Maximal suppression of insulin secretion to a level well below the baseline secretion rate was produced by 300 nM beta-endorphin (1.9 +/- 0.3 microU/islet.h). The first 15 min of glucose-stimulated insulin secretion was 6 times less sensitive to the inhibitory effect of beta-endorphin than was the next 45 min. The concentrations of beta-endorphin causing 50% inhibition of glucose-stimulated insulin secretion (IC50) for the 5- to 15-, 20- to 60-, and 5- to 60-min intervals were 1.96, 0.35, and 0.57 nM, respectively. Naloxone (3 microM) had no effect on glucose-stimulated insulin secretion, but partially antagonized the inhibitory effect of 30 nM beta-endorphin (10.2 +/- 2.9 microU/islet.h naloxone plus beta-endorphin vs. 2.6 +/- 1.1 microU/islet.h beta-endorphin; P less than 0.05). These data demonstrate that beta-endorphin, at low concentrations, has a direct inhibitory effect on insulin secretion, and they support the idea that a naloxone-sensitive beta-endorphin-binding component is present in pancreatic islets.