Release of β-endorphin by prostaglandin E2 to lower plasma glucose in streptozotocin-induced diabetic rats

In the present study, Wistar rats, which received a strepto-zotocin injection to induce diabetes (STZ-diabetic rats), a model similar to insulin-dependent diabetes mellitus (IDDM) or type 1 diabetes mellitus, were used to investigate the effect of prostaglandin (PG) E-2 on plasma glucose. Intravenous injection of PGE(2) produced a dose-dependent lowering of plasma glucose level in fasting STZ-diabetic rats after 60 min. In addition to the blockade of this hypoglycemic effect by guanethidine (a noradrenergic nerve terminal-blocking agent), prazosin at a dose effective to block al-adrenoceptors abolished the action of PGE(2). An increase of plasma norepinephrine (NE) was also observed in STZ-diabetic rats receiving PGE(2) injections. Participation of sympathetic stimulation by PGE(2) may thus be speculated. Also, the plasma glucose-lowering effect of PGE(2) was also blocked by pretreatment with naloxone or naloxonazine at doses sufficient to block opioid mu -receptor. Injection of PGE(2) increased plasma beta -endorphin-like immunoreactivity (BER) in STZ-diabetic rats, and this action was abolished by prazosin. Bilateral adrenalectomy resulted in the loss of this PGE(2) effect, and no increase was seen in plasma BER with PGE(2) in STZ-diabetic rats. Therefore, beta -endorphin from the adrenal gland appears to be responsible for the lowering of plasma glucose in STZ-diabetic rats by PGE(2) through an increase of NE release to activate alpha (1)-adrenoceptors.