Beta-endorphin-like Immunoreactivity Research Articles

Mediation of β-endorphin in andrographolide-induced plasma glucose-lowering action in type I diabetes-like animals

In the present study, we investigated the mechanism(s) for glucose-lowering action of andrographolide in streptozotocin-induced diabetic rats (STZ-diabetic rats). Andrographolide lowered plasma glucose concentrations in a dose-dependent manner and increased plasma beta-endorphin-like immunoreactivity (BER) dose-dependently in diabetic rats. Both of these responses to andrographolide were abolished by the pretreatment of animals with prazosin or N-(2-(2-cyclopropylmethoxy) ethyl) 5-choro-alpha-dimethyl-1H-indole-3-thylamine (RS17053) at doses sufficient to block alpha1-adrenoceptors (ARs). Also, andrographolide enhanced BER release from isolated rat adrenal medulla in a concentration-related manner that could be abolished by alpha1-ARs antagonists. Bilateral adrenalectomy in STZ-diabetic rats eliminated the activities of andrographolide, including the plasma glucose-lowering effect and the plasma BER-elevating effect. Andrographolide failed to lower plasma glucose in the presence of opioid micro-receptor antagonists and in the opioid micro-receptor knockout diabetic mice. Treatment of STZ-diabetic rats with andrographolide resulted in the reduced expression of phosphoenolpyruvate carboxykinase (PEPCK) in liver and an increased expression of the glucose transporter subtype 4 (GLUT 4) in soleus muscle. These effects were also blocked by opioid micro-receptor antagonists. In conclusion, our results suggest that andrographolide may activate alpha1-ARs to enhance the secretion of beta-endorphin which can stimulate the opioid micro-receptors to reduce hepatic gluconeogenesis and to enhance the glucose uptake in soleus muscle, resulting in a decrease of plasma glucose in STZ-diabetic rats. However, the roles of other endogenous opioid peptides or the mixture of several opioid peptides in the activation of opioid micro-receptors associated with the plasma glucose-lowering action of andrographolide, should be considered and need more investigation in the future.

Increase of β-Endorphin Secretion by Syringin, an Active Principle of Eleutherococcus senticosus, to Produce Antihyperglycemic Action in Type 1-like Diabetic Rats

We employed streptozotocin-induced diabetic rats (STZ-diabetic rats) as type 1 diabetes-like animal models to investigate the mechanism(s) of antihyperglycemic action produced by syringin, an active principle purified from the rhizome and root part S of ELEUTHEROCOCCUS SENTICOSUS (Araliaceae). Bolus intravenous (i. v.) injection of syringin dose-dependently decreased the plasma glucose of STZ-diabetic rats in 30 minutes in a way parallel to the increase of plasma beta-endorphin-like immunoreactivity (BER). Syringin enhanced BER release from the isolated adrenal medulla of STZ-diabetic rats in a concentration-dependent manner from 0.001 to 10 micromol/l. Bilateral adrenalectomy in STZ-diabetic rats eliminated the activities of syringin (1 mg/kg, i. v.) including the plasma glucose-lowering effect and the plasma BER-elevating effect. Also, syringin failed to lower plasma glucose in the presence of micro-opioid receptor antagonists and/or in the micro-opioid receptor knockout diabetic mice. In conclusion, the obtained results suggest that syringin can enhance the secretion of beta-endorphin from adrenal medulla to stimulate peripheral micro-opioid receptors resulting in a decrease of plasma glucose in diabetic rats lacking insulin.

Mechanism for blockade of angiotensin subtype 1 receptors to lower plasma glucose in streptozotocin‐induced diabetic rats

We investigated the mechanism(s) by which valsartan, a selective antagonist of angiotensin subtype 1 (AT(1)) receptor, decreased plasma glucose in streptozotocin (STZ)-induced diabetic rats. The plasma glucose concentration was assessed by the glucose oxidase method. The concentration of beta-endorphin in plasma or medium incubating adrenal medulla was measured using an enzyme-linked immunosorbent assay. The mRNA levels of the subtype 4 form of glucose transporter (GLUT4) in soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK) in the liver were detected by Northern blotting analysis, while the protein levels of GLUT4 in isolated soleus muscle and hepatic PEPCK were investigated using Western blotting analysis. A single intravenous injection of valsartan dose-dependently increased plasma beta-endorphin-like immunoreactivity (BER) in parallel with the lowering of plasma glucose concentration in STZ-induced diabetic rats. Naloxone and naloxonazine inhibited the plasma glucose-lowering action of valsartan at doses sufficient to block opioid micro-receptors. In contrast to its action in wild-type diabetic mice, valsartan failed to modify plasma glucose in opioid micro-receptor knockout diabetic mice. Bilateral adrenalectomy in STZ-induced diabetic rats eliminated both the plasma glucose-lowering action and the plasma BER-elevating action of valsartan. In the isolated adrenal medulla of STZ-induced diabetic rats, angiotensin II (Ang II) or valsartan did not affect spontaneous BER secretion. Activation of cholinergic receptors by 1.0 micromol/l acetylcholine (ACh) enhanced BER secretion from the isolated adrenal medulla of STZ-induced diabetic rats, but not in the presence of 1.0 nmol/l Ang II, while valsartan reversed this inhibition by Ang II in a concentration-dependent manner. Treatment of STZ-induced diabetic rats with valsartan (0.2 mg/kg) three times daily for 3 days resulted in an increase in gene expression of GLUT4 in soleus muscle and impeded the reduction of elevated mRNA or protein level of hepatic PEPCK. Both of these effects were blocked by opioid micro-receptor antagonist. The results suggest that blockade of AT(1) receptor by valsartan may enhance the adrenal beta-endorphin secretion induced by ACh, activating the opioid micro-receptors to increase glucose utilization and/or to decrease hepatic gluconeogenesis, resulting in the reduction of plasma glucose in STZ-induced diabetic rats.

Metformin Increases Insulin Sensitivity and Plasma β-endorphin in Human Subjects

Metformin has been widely used in clinical type 2 diabetes treatment and prevention. The present study was designed to explore the effect on people with a sedentary lifestyle at therapeutic doses. Twenty-two physically-inactive volunteers with normal glucose tolerance were studied. Escalating doses of metformin in low-dose (250 mg), intermediate-dose (500 mg), and high-dose (750 mg) treatment three times per day were administrated into each subject for a three-week treatment period. Fasting plasma glucose, A1C, HOMA-IR for insulin resistance, lipid profile, and plasma beta-endorphin-like immunoreactivity (BER) were measured before treatment and weekly at the end of each dosing period. Metformin significantly reduced fasting plasma glucose and HOMA-IR in healthy humans after receiving this treatment at therapeutic doses including low-dose (5 %, 17 %), intermediate-dose (6 %, 25 %) and high-dose treatment (6 %, 21 %). Plasma BER was also increased from 135.46 +/- 61.73 pg/ml to 137.52 +/- 66.11 pg/ml by low-dosing (p = 0.39), to 139.17 +/- 64.08 pg/ml by intermediate-dosing (p = 0.32), and to 149.59 +/- 63.32 pg/ml by high-dosing (p < 0.05). Also, serum cholesterol decreased significantly using metformin at therapeutic doses including low-dose (4 %), intermediate-dose (8 %) and high-dose treatment (7 %). However, metformin failed to modify levels of serum HDL-cholesterol and C-reactive protein (CRP) in healthy subjects. Also, the reduction of serum cholesterol by metformin did not correlate to the increase in insulin sensitivity. In conclusion, metformin causes a significant parallel increase in insulin sensitivity and plasma beta-endorphin level in human subjects.

Mediation of beta-endorphin by the isoflavone puerarin to lower plasma glucose in streptozotocin-induced diabetic rats.

We investigate the mechanism(s) of plasma glucose lowering action of puerarin in streptozotocin-induced diabetic rats (STZ-diabetic rats). Puerarin at the effective dosage to lower higher plasma glucose increased plasma beta-endorphin-like immunoreactivity (BER) in STZ-diabetic rats. Both effects of puerarin were abolished by the pretreatment with prazosin. Also, puerarin enhanced BER release from isolated rat adrenal medulla in a concentration-dependent manner that can be abolished by prazosin. Moreover, bilateral adrenalectomy in STZ-diabetic rats eliminated the actions of puerarin including the plasma glucose lowering effect and plasma BER elevating effect. In addition, naloxone and naloxonazine inhibited the plasma glucose lowering action of puerarin. Unlike in wild-type diabetic mice, puerarin failed to lower the plasma glucose in opioid micro-receptor knockout diabetic mice. In conclusion, our results suggest that puerarin may activate alpha (1)-adrenoceptors on the adrenal gland to enhance the secretion of beta-endorphin to result in a decrease of plasma glucose in STZ-diabetic rats.

Mediation of beta-endorphin by isoferulic acid to lower plasma glucose in streptozotocin-induced diabetic rats.

We investigated the mechanism(s) by which isoferulic acid lowers plasma glucose levels in streptozotocin-induced diabetic rats (STZ-diabetic rats). In STZ-diabetic rats, isoferulic acid dose dependently lowered plasma glucose concentrations and increased plasma beta-endorphin-like immunoreactivity (BER). Both of these effects of isoferulic acid were abolished by pretreatment of rats with tamsulosin or 2-[2,6-dimethoxyphenoxyethyl]aminomethyl-1,4-benzodioxane hydrochloride (WB 4101) at doses sufficient to block alpha1-adrenoceptors. Also, isoferulic acid enhanced BER release from isolated rat adrenal medulla in a concentration-dependent manner that could be abolished by treatment with alpha1-adrenoceptor antagonists. Moreover, bilateral adrenalectomy in STZ-diabetic rats eliminated the activities of isoferulic acid, including the plasma glucose-lowering effect and the plasma BER-elevating effect. Naloxone and naloxonazine inhibited the plasma glucose-lowering activity of isoferulic acid at doses sufficient to block opioid mu-receptors. In contrast with the effect in wild-type diabetic mice, isoferulic acid failed to lower plasma glucose levels in opioid mu-receptor knockout diabetic mice. Treatment of STZ-diabetic rats with isoferulic acid three times in 1 day resulted in an increase in the expression of the glucose transporter subtype 4 form in soleus muscle. This effect was blocked by alpha1-adrenoceptor or opioid mu-receptor antagonists. The reduction of elevated mRNA or protein level of hepatic phosphoenolpyruvate carboxykinase was also impeded in the same groups of STZ-diabetic rats. In conclusion, our results suggest that isoferulic acid may activate alpha1-adrenoceptors to enhance the secretion of beta-endorphin, which can stimulate the opioid mu-receptors to increase glucose use or/and reduce hepatic gluconeogenesis, resulting in a decrease of plasma glucose in STZ-diabetic rats.

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

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.

Beta endorphin-like immunoreactivity in human aqueous humor and crystalline lens

We measured the concentration of β-endorphin (β-End) in plasma, as well as in aqueous humor and crystalline lens removed during cataract surgery. β-End was detected both in the aqueous humor and in the crystalline lens. The concentration of β-End in the aqueous humor corresponded to almost the half of the plasma level (2.18 fmol/l and 4.55 fmol/l). Endogenous β-End is presumed to enter the intraocular structures by passive diffusion.

ANF(1-28) is a potent suppressor of pro-opiomelanocortin (POMC) mRNA but a weak inhibitor of beta EP-LI release from AtT-20 cells.

Controversies remain whether atrial natriuretic factor (ANF) may play a role in modulating the release of POMC derived peptides from pituitary corticotrophs. Employing AtT-20 mouse pituitary tumour cells, we report here the effects of rat ANF(1-28) and sodium nitroprusside (SNP), both of which augment cellular levels of cGMP through activating particulate and soluble guanylyl cyclases respectively, on the expression of POMC mRNA abundance. Furthermore, the cellular contents and secretion of (beta endorphin-like immunoreactivity) beta EP-LI from these cultures were also examined. Whereas the abundance of POMC mRNA was found to be markedly suppressed following 4h of incubation with rANP(1-28) (0.01 to 1 microM), SNP (0.1 to 10 microM) and dibutyryl-cGMP (1 to 100 microM) in a dose related manner, only a modest reduction in the release and cell contents of beta EP-LI was found in some of these cultures. It is also of interest to note that in all the cases examined, the inhibitory effect was associated with a significant suppression of cAMP levels in the cultures. Taken together, our present findings suggest that ANF may play a more important role in suppressing the production than the release of POMC related peptides from AtT-20 cells. Thus, it raises the possibility that hypothalamic ANF may likewise modulate the function of the pituitary-adrenal axis through exerting a greater effect on inhibiting the production than the secretion of pituitary ACTH.

Hormonal responses to fighting in hamsters: Separation of physical and psychological causes

Male Syrian hamsters were paired and allowed to interact with a conspecific for 15 min a day for 4 days. On the fifth day, the animals were again paired, but they were kept physically separated by a mesh partition that allowed visual, olfactory, and auditory contact between the animals. Controls were placed with conspecifics on each of the 5 testing days, but the partition between them was never removed. Hamsters that were submissive on days 1–4 exhibited elevated plasma adrenocorticotropin-like immunoreactivity (ACTH-LI), beta-endorphin-like immunoreactivity (B-EP-LI), and cortisol on day 5 even though no fighting occurred on that day. Dominant hamsters did not differ from controls. These data support the hypothesis that there is an important psychological component to the pituitary-adrenocortical response in defeated hamsters.

Effect of anaesthetics on the release of beta-endorphin-immunoreactivity in rat plasma

Analgesia and anaesthesia produced by fentanyl, urethane and ether, but not pentobarbital, occured concomitantly with an increase in the concentration of plasma beta-endorphin like immunoreactivity (BEIR), probably of pituitary origin. This increase was not associated with significant changes in pituitary or brainstem beta-endorphin content. Pretreatment with naloxone caused a reduction in plasma BEIR increase following Hypnorm R, ether and urethane; and in the analgesia following Hypnorm R and urethane. Pentobarbital, alone or in combination with naloxone, did not increase the concentration of plasma beta-endorphin. These results may indicate participation of endogenous opioids in the mechanism of action of urethane.

Cerebrospinal Fluid and Plasma Beta-Endorphin-Like Immunoreactivity in Full-Term Neonates and in Preterm Neonates with and without Apnea of Prematurity

Beta-endorphin-like immunoreactivity (B-ELI) was measured in cerebrospinal fluid (CSF) and plasma from infants of postnatal age 24 h to 70 days. Three groups were examined: 17 were of postconceptual age greater than or equal to 37 weeks, 16 were postconceptual age less than or equal to 35 weeks without apnea and 10 were of postconceptual age less than or equal to 35 weeks with apnea. All infants were clinically stable. Two-way analysis of variance between groups showed no difference in the concentration of B-ELI in CSF or plasma, or in the CSF/plasma B-ELI ratio. Concentrations of B-ELI in plasma were significantly higher in infants of postnatal age 1-3 weeks and greater than or equal to 4 weeks, than in infants of postnatal age less than 1 week. We conclude that, in nonstressed infants, there is no relationship between the concentration of B-ELI in CSF or plasma and a concurrent diagnosis of apnea of prematurity. Our data indicate that a significant developmental increase occurs in the plasma concentration of B-ELI after the first week of life.

Proopiomelanocortin opioids in brain, CSF, and plasma of piglets during hypoxia.

beta-Endorphin-like immunoreactivity (BELI), containing the biologically active beta-endorphin, its precursor beta-lipotropin (BLP), and deactivated product N-acetyl-beta-endorphin (ABE), were measured by radioimmunoassay in plasma, cerebrospinal fluid (CSF), and in a dorsal medullary slice containing the respiratory-related nucleus tractus solitarius (dmscNTS) of young and older piglets in normoxia and hypoxia. Significant increase with hypoxia occurred in the levels of BLP in the plasma and CSF and of BELI and ABE in the plasma of the young group. In the older group, such increases occurred in ABE levels of the dmscNTS, in BLP and ABE levels of the CSF, and in plasma BELI. Estimated levels of pure beta-endorphin were higher in the CSF of young piglets during both control and hypoxia. With hypoxia, these estimated levels increased significantly in the plasma of the young age group but showed only a borderline increase in the old group. It is possible that higher opioid levels in the CSF of young as compared with older neonates, enhanced by a greater opioid increase in their plasma during hypoxia, may help explain the suppressed respiratory response to hypoxia of the newborn.

Effect of cisapride on the concentrations of β-endorphinlike immunoreactivity and substance P-like immunoreactivity in the rat gastrointestinal tract

Cisapride is a gastrointestinal prokinetic agent reported to be devoid of direct cholinergic effect from the myenteric plexus of the gut. The effect of cisapride (0.125, 0.5, 2mg/kg, i.p.) on the concentration beta-endorphin and substance P in rat gastrointestinal tract was studied. beta-Endorphinlike immunoreactivity contents were significantly increased in both mucosal and muscular layers of the entire gastrointestinal tract (from gastric body to rectum) of the rats treated with 2 mg/kg of cisapride. beta-Endorphinlike immunoreactivity contents were also increased in a part of the gastrointestinal tract of the rats treated with 0.125 or 0.5 mg/kg of cisapride. Substance P like immunoreactivity contents were significantly decreased in muscular layers of the rectosigmoid colon of the rats treated with 2 mg/kg of cisapride. This study suggests that the prokinetic effects of cisapride may relate to the contents of beta-endorphinlike immunoreactivity and substance P like immunoreactivity in gastrointestinal tract.

Central alpha 2-adrenergic stimulation increases neurointermediate lobe immunoreactive beta-endorphin in spontaneously hypertensive rats.

A possible influence of the central alpha 2-adrenergic system on beta-endorphin was examined in rat anterior pituitary, neurointermediate lobe, and plasma. The concentration of beta-endorphin in anterior pituitary, neurointermediate lobe, and plasma was determined by radioimmunoassay 15 minutes after subcutaneous injection of clonidine in 14-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Clonidine reduced the concentration of the plasma beta-endorphinlike immunoreactivity in SHR and to a lesser extent in WKY. No significant changes in the concentration of beta-endorphinlike immunoreactivity were observed in anterior pituitary. Clonidine increased the concentration of neurointermediate lobe beta-endorphinlike immunoreactivity in SHR in a dose-related manner but did not affect the concentration in WKY. Administration of yohimbine (1 mg/kg) completely blocked the clonidine-induced increase of neurointermediate lobe beta-endorphinlike immunoreactivity in SHR, while prazosin (1 mg/kg) had no effect. These data suggest that the central alpha 2-adrenergic activation increases the neurointermediate lobe concentration of beta-endorphinlike immunoreactivity in SHR by suppressing beta-endorphin release from the neurointermediate lobe into the circulation.

Haloperidol increases plasma beta endorphin-like immunoreactivity and cortisol in normal human males

To investigate possible central dopaminergic regulation of betaendorphin-like immunoreactivity (βE-LI) and adrenocorticotropin (ACTH) release in humans, we gave the dopamine antagonist haloperidol or placebo intravenously to twelve normal male subjects and measured βE-LI and cortisol for 120 minutes following injection. Haloperidol, but not placebo, produced significant increases in plasma βE-LI and cortisol. These findings suggest that central dopaminergic pathways such as the tuberohypophyseal system may participate in regulation of the secretion of βE and ACTH from the human pituitary.

Apgar Scores and Cerebrospinal Fluid BetaEndorphin-like Immunoreactivity During the First Day of Life. Preliminary Obervations

Apgar Scores and Cerebrospinal Fluid BetaEndorphin-like Immunoreactivity During the First Day of Life. Preliminary Obervations

Apgar scores and cerebrospinal fluid beta-endorphinlike immunoreactivity during the first day of life. Preliminary observations.

beta-Endorphinlike Immunoreactivity (BLI) was measured in sterile, bloodless samples of cerebrospinal fluid (CSF) during the first 24 hours of life in order to assess the relationship between perinatal asphyxia and endogenous opioid activity within the central nervous system. The median CSF BLI in infants with one-minute Apgar scores of 1 to 4 was 148 pg/mL (range, 96 to 171 pg/mL) and that of infants with Apgar scores of 5 to 9 was 78 pg/mL (range, 25 to 162 pg/mL). The linear regression equation correlating CSF BLI with one-minute Apgar score was y = -10.7x + 169.1. Our findings of a highly significant inverse correlation between one-minute Apgar scores and CSF BLI support the hypothesis that perinatal asphyxia is associated with increased activity of opioid systems in the central nervous system.

Peripheral beta endorphin-like immunoreactivity in cirrhosis with ascites

Peripheral beta endorphin-like immunoreactivity in cirrhosis with ascites

Apgar Scores and Cerebrospinal Fluid BetaEndorphin-like Immunoreactivity During the First Day of Life. Preliminary Obervations

Apgar Scores and Cerebrospinal Fluid BetaEndorphin-like Immunoreactivity During the First Day of Life. Preliminary Obervations