Inhibition of insulin release by scorpion toxin in rat pancreatic islets

Toxin purified from venom of the scorpion Leiurus quinquestriatus was used to release norepinephrine from adrenergic nerve terminals in isolated pancreatic islets perifused in vitro. Addition of toxin (10 μg./ml.) to the perifusion medium caused a sixfold increase in release of norepinephrine in the presence or absence of 3 x 10^-5M phenoxybenzamine. During 20 minutes of stimulation with toxin, the pancreatic islets released an average of 15 pg. of norepinephrine per islet, which represented 20 percent of the normal content of norepinephrine in islets. Insulin secretory rates in response to either 1.0 or 3.0 mg./ml. glucose were inhibited similarly by scorpion toxin. Addition of phenoxybenzamine abolished the inhibition of insulin release caused by scorpion toxin. Phenoxybenzamine alone did not affect release of insulin. Neither the enhanced release of norepinephrine nor the decreased release of insulin was reversed by a 20 minute wash out period after infusion of toxin. These results indicate that the sympathetic nerve terminals in the rat pancreatic islet contain considerable amounts of norepinephrine that can be released by scorpion toxin. The norepinephrine released from sympathetic nerve endings in the pancreatic islet can inhibit release of insulin through an alpha adrenergic action that is blocked by phenoxybenzamine.