Effects of beta-endorphin, met-enkephalin, and dynorphin A on basal and stimulated insulin secretion in the mouse.
Since opioid peptides and opiate receptors have been demonstrated in the pancreatic islets, we investigated the effects of beta-endorphin, met-enkephalin, 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 mumol/kg), or terbutaline (beta 2-adrenoceptor agonist, 3.6 mumol/kg). It was found that beta-endorphin, met-enkephalin, and dynorphin A were all without effect on basal plasma insulin levels, except a slight elevation by beta-endorphin induced at 2 min after its injection at 64 nmol/kg (to 41 +/- 2 microU/mL vs 28 +/- 4 microU/mL in controls; p less than 0.05). Glucose- and terbutaline-induced insulin secretion were inhibited by beta-endorphin at the lower dose levels of 0.25 (p less than 0.01) and 1 nmol/kg (p less than 0.05). This effect was counteracted by the opiate receptor antagonist naloxone (500 micrograms/kg). In contrast, beta-endorphin at the high dose levels of 16 and 64 nmol/kg augmented the glucose- and terbutaline-induced insulin secretion (p less than 0.05). Carbachol-induced insulin secretion was not affected by beta-endorphin at the lower dose levels but augmented by the peptide at 64 nmol/kg (p less than 0.01). Met-enkephalin inhibited glucose- (p less than 0.01) and terbutaline- (p less than 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. beta-Endorphin at low dose levels inhibits and at high dose levels augments stimulated insulin secretion; 2. Met-enkephalin inhibits stimulated insulin secretion; and 3. Dynorphin A does not affect insulin secretion. It is suggested that the main influence of beta-endorphin and met-enkephalin under in vivo conditions in the mouse is to inhibit stimulated insulin secretion.
Ahrén
B
B
Department of Pharmacology, Lund University, Sweden.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D004399:Dynorphins / Q000494:pharmacology*; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D012016:Reference Values; D013726:Terbutaline / Q000494:pharmacology; D001615:beta-Endorphin / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D004744:Enkephalin, Methionine; D001615:beta-Endorphin; D004399:Dynorphins; D002217:Carbachol; D005947:Glucose; D013726:Terbutaline