Opioid peptide effects on insulin release and c-AMP in islets of Langerhans

The time course and specificity of the effect of opioid peptides on c-AMP production in the islets of Langerhans was examined. An enkephalin analogue, d-Ala2Me Phe4 Met(O)-ol enkephalin (DAMME, Sandoz) produced a significant stimulation of basal c-AMP levels, with a peak of stimulation at 5 minutes and a decline thereafter. These changes in intracellular c-AMP levels were of the same order of magnitude as those induced by other secretagogues, but did not coincide in time with the more rapid peak of enkephalin-induced insulin release. The rise in islet c-AMP and insulin secretion induced by DAMME and alpha-endorphin but not leu enkephalin was antagonised by naloxone. The effects of high and low concentrations of a variety of opioid peptides and naloxone on insulin release and islet c-AMP levels were determined, alpha-endorphin, dynorphin, leu enkephalin and met enkephalin all stimulated insulin secretion significantly, though not to the same extent. Higher concentrations of alpha-endorphin, dynorphin and met enkephalin inhibited insulin release relative to effects at low opiate concentrations. However, higher concentrations of leu enkephalin stimulated insulin release further. We conclude from these results that the mode of action of opioid peptides in stimulating insulin release is not via increased islet c-AMP exclusively. Furthermore, the results obtained with different classes of opioid suggest the presence of distinctive types of opiate receptor in islets of Langerhans.