Role of mu-opioid receptors in insulin release in the presence of inhibitory and excitatory secretagogues.
In mouse pancreatic islets incubated under static conditions, the inhibitory effects on glucose-evoked insulin release induced by adrenaline (1 microM), clonidine (2 microM) and UK 14,304 (brimonidine, 0.001-1 microM) were abolished by naloxone (30 nM). Only CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH(2), 0.1 microM), a very selective mu-opioid receptor antagonist, blocked the response to UK 14,304. Glucose-induced insulin secretion was attenuated by both beta-endorphin (0.01 microM) and endomorphin-1 (0.1 microM). Naloxone and CTOP prevented these inhibitory responses. The stimulatory effect of glibenclamide (1 microM) was also reduced by endomorphin-1. However, when islets were incubated in the presence of K(+) (30 mM), carbachol (100 microM) or forskolin (0.1 microM), neither the inhibitory effect induced by UK 14,304 was reversed by naloxone, nor endomorphin-1 altered the responses promoted by the excitatory agents. Thus, alpha(2)-adrenoceptor stimulation might inhibit glucose-induced insulin secretion by releasing endogenous opioids. Mu-Opioid receptor activation and opening of K(ATP) channels could be involved in the response.
Department of Physiology and Pharmacology, School of Medicine, University of Salamanca, Avda. de Alfonso X El Sabio s/n, 37007 Salamanca, Spain. barrado@usal.es
María José
MJ
García-Barrado
María Carmen
MC
Iglesias-Osma
Raquel
R
Rodríguez
Mariano
M
Martín
Julio
J
Moratinos
D058647:Adrenergic alpha-2 Receptor Agonists; D000818:Animals; D000068438:Brimonidine Tartrate; D003000:Clonidine / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology
D058647:Adrenergic alpha-2 Receptor Agonists; D007328:Insulin; D011810:Quinoxalines; D017450:Receptors, Opioid, mu; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D009270:Naloxone; D000068438:Brimonidine Tartrate; D013004:Somatostatin; D003000:Clonidine; D005905:Glyburide