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.
Copyright 2002 Elsevier Science B.V.