Since opioid peptides and opiate receptors have been demonstrated in the pancreatic islets, we investigated the effects of β-endorphin, metenkephalin, and dynorphin A, on basal and stimulated insulin secretion in the mouse. Each of the three opioid peptides was injected intravenously (0.06-64 nmol/kg) alone or together with each of the three insulin releasing agents glucose (2.8 mmol/kg), carbachol (cholinergic agonist, 0.16 µmol/kg), or terbutaline (β₂-adrenoceptor agonist, 3.6 µmol/kg). It was found that β-endorphin, met-enkephalin, and dynorphin A were all without effect on basal plasma insulin levels, except a slight elevation by β -endorphin induced at 2 min after its injection at 64 nmol/kg (to 41 ±2 µU/mL vs 28±4 µU/mL in controls; p<0.05). Glucose- and terbutaline-induced insulin secretion were inhibited by µ-endorphin at the lower dose levels of 0.25 (p<0.01) and 1 nmol/kg (p<0.05). This effect was counteracted by the opiate receptor antagonist naloxone (500 µg/kg). In contrast, β-endorphin at the high dose levels of 16 and 64 nmol/kg augmented the glucose- and terbutaline-induced insulin secretion (p<0.05). Carbacholinduced insulin secretion was not affected by β-endorphin at the lower dose levels but augmented by the peptide at 64 nmol/kg (p<0.01). Metenkephalin inhibited glucose- (p<0.01) and terbutaline- (p<0.05) induced insulin secretion at the high dose rates of 16 and 64 nmol/kg, but the peptide was without effect on carbachol-induced insulin secretion. The inhibitory effects were counteracted by naloxone. Dynorphin A did not affect stimulated insulin secretion at any of the dose levels tested. In summary, in the mouse

1. 1.
   β-Endorphin at low dose levels inhibits and at high dose levels augments stimulated insulin secretion;
2. 2.
   Met-enkephalin inhibits stimulated insulin secretion; and
3. 3.
   Dynorphin A does not affect insulin secretion.

It is suggested that the main influence of β-endorphin and met-enkephalin under in vivo conditions in the mouse is to inhibit stimulated insulin secretion.