Release of β-Endorphin by Prostaglandin E2 to Lower Plasma Glucose in Streptozotocin-Induced Diabetic Rats

Abstract

In the present study, Wistar rats, which received a streptozotocin 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) E2 on plasma glucose. Intravenous injection of PGE2 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 alpha1-adrenoceptors abolished the action of PGE2. An increase of plasma norepinephrine (NE) was also observed in STZ-diabetic rats receiving PGE2 injections. Participation of sympathetic stimulation by PGE2 may thus be speculated. Also, the plasma glucose-lowering effect of PGE2 was also blocked by pretreatment with naloxone or naloxonazine at doses sufficient to block opioid mu-receptor. Injection of PGE2 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 PGE2 effect, and no increase was seen in plasma BER with PGE2 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 PGE2 through an increase of NE release to activate alpha1-adrenoceptors.

Mediation of β-Endorphin by Isoferulic Acid to Lower Plasma Glucose in Streptozotocin-Induced Diabetic Rats

“…The plasma glucoselowering activity of isoferulic acid was abolished in STZdiabetic rats after bilateral adrenalectomy. Similar to previous reports (Koenig et al, 1986;Cheng et al, 2001a), the basal plasma level of BER in STZ-diabetic rats that received bilateral adrenalectomy was not different from that in shamoperated controls. Moreover, no increase in the plasma BER level was obtained in these adrenalectomized diabetic rats after treatment with isoferulic acid at the effective doses.…”

Mediation of Endogenous β‐Endorphin by Tetrandrine to Lower Plasma Glucose in Streptozotocin‐Induced Diabetic Rats

“…The basal plasma BER was not significantly different in STZ-diabetic rats that received adrenalectomy as compared with the sham-operated group; these results are consistent with our previous data (18). However, both the decrease in plasma glucose and the increase in plasma BER induced by tetrandrine (1.0 mg/kg) were not observed in STZ-diabetic rats with bilateral adrenalectomy, while these effects persisted in the sham-operated STZ-diabetic rats (Table 2).…”

“…In fact, plasma glucose-lowering activity is not entirely dependent on insulin regulation; for example, physical exercise is traditionally considered beneficial in the treatment of diabetes (21). In addition, our previous reports (16,18,19,22) indicated that activation of opioid μ-receptors plays a role in the regulation of glucose metabolism during an insulin-deficient state. The physiological actions of endogenous β-endorphins are mediated in part by opioid μ-receptors (23).…”

Serotonin enhances β-endorphin secretion to lower plasma glucose in streptozotocin-induced diabetic rats

“…Blood samples were then centrifuged at 13,000 rpm for 3 min, and an aliquot (10 μl) of plasma was added to 1.0 ml of Glucose Kit Reagent (Biosystems S.A., Barcelona, Spain) and incubated at 37°C in a water bath (Yamato-BT-25, Tokyo, Japan) for 5 min. The concentration of plasma glucose was then estimated via an analyzer (Biosystems 330, Barcelona, Spain) with samples run in duplicate (Forman et al, 1988;Cheng et al, 2001).…”

“…Bilateral adrenalectomy was performed in Wistar rats as described previously (Cheng et al, 2001) using the dorsal approach under pentobarbital anesthesia (30.0 mg/kg, i.p.). Sham-operated animals served as controls.…”