beta-endorphin and Hypoglycemia

β-Endorphin release in response to recurrent hypoglycemia is implicated in the pathogenesis of hypoglycemia-associated autonomic failure.. We hypothesized that exercise-induced β-endorphin release will also result in the deterioration of subsequent hypoglycemia counterregulation and that the counterregulatory response will negatively correlate with the degree of antecedent β-endorphin elevation.. Sixteen healthy subjects (six females, aged 26 ± 4.3 yr, body mass index 26.1 ± 5.6 kg/m(2)) were studied with three experimental paradigms on 2 consecutive days. Day 1 consisted of one of the following: 1) two 90-min hyperinsulinemic hypoglycemic clamps (3.3 mmol/liter); 2) two 90-min hyperinsulinemic euglycemic clamps while subjects exercised at 60% maximal oxygen uptake; or 3) two 90-min hyperinsulinemic euglycemic clamps (control). Day 2 followed with hyperinsulinemic (396 ± 7 pmol/liter) stepped hypoglycemic clamps (5.0, 4.4, 3.9, and 3.3 mmol/liter plasma glucose steps).. Day 2 hypoglycemia counterregulatory hormonal response and glucose turnover ([3-(3)H]-glucose) as indicators of recovery from hypoglycemia.. There was a significant inverse correlation between plasma β-endorphin levels during exercise and catecholamine release during subsequent hypoglycemia. Subjects with an exercise-induced rise in β-endorphin levels to above 25 pg/ml (n = 7) exhibited markedly reduced levels of plasma epinephrine and norepinephrine compared with control (2495 ± 306 vs. 4810 ± 617 pmol/liter and 1.9 ± 0.3 vs. 2.9 ± 0.4 nmol/liter, respectively, P < 0.01 for both). The rate of endogenous glucose production recovery in this group was also much lower than in controls (42 vs. 89%, P < 0.01).. The physiological increase in β-endorphin levels during exercise is associated with the attenuation of counterregulation during subsequent hypoglycemia.

Topics: Adult; beta-Endorphin; Blood Glucose; Exercise; Feedback, Physiological; Female; Glucagon; Humans; Hypoglycemia; Insulin; Male; Norepinephrine; Time Factors; Young Adult

It has been demonstrated that beta-endorphin reduces CRH production and hypoglycaemia-induced ACTH secretion in the rat. We aimed to determine whether supraphysiological levels of beta-endorphin inhibit the ACTH and CRH response to insulin-induced hypoglycaemia in human subjects.. Plasma glucose, prolactin, cortisol, ACTH, CRH and AVP were measured at intervals over a 3-hour period. Intravenous beta-endorphin 5 mg/50 ml or an equal volume of normal saline was infused between 30 and 90 minutes, with soluble insulin 0.15 units/kg administered i.v. at 60 minutes in a cross-over design.. Six healthy male volunteers aged 20-35 years.. Prolactin was measured by a fluoroimmunometric assay, ACTH, CRH and AVP by radioimmunoassay, and cortisol was measured by enzyme-linked immunosorbent assay. Haemodynamic measurements were recorded prior to each blood sample. Results are expressed as mean +/- standard error of the mean.. beta-Endorphin resulted in a significant decrease in baseline cortisol (P < 0.05) but not ACTH. Plasma glucose (P < 0.001) and CRH (P < 0.05) and PRL (P < 0.05) increased significantly during beta-endorphin compared to normal saline. After insulin administration, glucose reached a similar nadir during beta-endorphin and normal saline (2.1 +/- 0.1 and 1.9 +/- 0.15 mmol/l, respectively) but the fall in plasma glucose was delayed during beta-endorphin (P < 0.01 by ANOVA). This resulted in a significantly altered time-course for the ACTH and cortisol responses (P < 0.05 for each), but no difference overall in the magnitude of the response. In contrast, neither the timing nor the magnitude of the CRH and AVP responses were affected. Prolactin also reached a similar peak value after the administration of insulin, while the haemodynamic responses to hypoglycaemia were not significantly altered during beta-endorphin.. While beta-endorphin has been shown to be inhibitory to basal ACTH and cortisol secretion in humans, we note a significant increase in plasma CRH in response to beta-endorphin, which may be arising from a peripheral source. Intravenous beta-endorphin increases plasma glucose and delays the onset of hypoglycaemia following insulin but does not result in significant inhibition of the ACTH and cortisol response. This may reflect the poor penetration of beta-endorphin into the central nervous system, although a hypothalamic effect of beta-endorphin is implied by the increased PRL. The significantly delayed time course in ACTH and cortisol secretion noted during beta-endorphin is not explained by a later response of either CRH or AVP. Although peripheral levels of these hormones may be a relatively insensitive measure of hypothalamic function, an additional factor may influence ACTH release during hypoglycaemia.

Topics: Adrenocorticotropic Hormone; Adult; Arginine Vasopressin; beta-Endorphin; Blood Glucose; Corticotropin-Releasing Hormone; Humans; Hydrocortisone; Hypoglycemia; Hypothalamo-Hypophyseal System; Insulin; Male; Pituitary-Adrenal System; Prolactin; Time Factors

Nutritional factors, such as an excess or a deficiency of glucose, play an important role in neuroendocrine regulations. Hormonal and metabolic responses to hypoglycemia were examined in healthy non-obese volunteers under conditions of low ambient temperature. Hypoglycemia was induced by intravenous injection of insulin in two randomized trials performed at room temperature and at 4 degrees C. At room temperature, the typical neuroendocrine response to hypoglycemia was established. The increases of ACTH, beta-endorphin, growth hormone and cortisol in response to insulin hypoglycemia failed to be modified by low ambient temperature. Acute cold exposure significantly reduced epinephrine and totally inhibited prolactin response to insulin-induced hypoglycemia. In spite of significant changes in epinephrine response to hypoglycemia at low ambient temperature, no striking differences in plasma glucose levels compared to those measured at room temperature were observed. However, under conditions of low temperature the reestablishment of normoglycemia was delayed. No changes in free fatty acids were found under our experimental conditions. The presented data show that low ambient temperature exerts selective effects on some neuroendocrine and metabolic parameters.

Topics: Adrenocorticotropic Hormone; beta-Endorphin; Cold Temperature; Epinephrine; Growth Hormone; Humans; Hydrocortisone; Hypoglycemia; Insulin; Kinetics; Male; Neurosecretory Systems; Prolactin

Although pituitary hormones play only a minor role in acute hormonal counterregulation during insulin-induced hypoglycemia, their concomitant secretion with the profound sympathoadrenal response provides an indicator of hypothalamic-pituitary activation. The release of different amounts of beta-endorphin, growth hormone, and adrenocorticotropin during human (HI) and porcine (PI) insulin-induced hypoglycemia would serve as a pointer to a different insulin species effect on hypothalamic-pituitary response. We performed a controlled, double-blind study with randomization to either HI or PI to compare insulin effects during developing and established hypoglycemia. The glucose clamp technique was used to lower the blood glucose concentration stepwise (3.3, 2.2, 1.7 mmol/l) over similar periods in ten patients with insulin-dependent diabetes mellitus. beta-endorphin, growth hormone, and adrenocorticotropin levels were determined by radioimmunoassay from arterialized blood at the above plateaus. A different action of HI or PI on peripheral glucose metabolism was not found. Pituitary hormones increased significantly during hypoglycemia (analysis of variance for hypoglycemic effects: beta-endorphin, P < 0.02; growth hormone, P < 0.04; adrenocorticotropin, P < 0.05). No insulin species effect was detected. Hypothalamic-pituitary activation during insulin-induced hypoglycemia is independent of the insulin species used, which supports earlier observations of an identical sympathoadrenal response during HI- and PI-induced hypoglycemia.

Topics: Adrenocorticotropic Hormone; Adult; Animals; beta-Endorphin; Blood Glucose; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Growth Hormone; Higher Nervous Activity; Humans; Hypoglycemia; Hypothalamo-Hypophyseal System; Insulin; Male; Pituitary-Adrenal System; Species Specificity; Swine

The present study investigated the possible effect of somatostatin and oxytocin on the basal and stress-induced rise of beta-endorphin (beta-END), beta-lipotrophin (beta-LPH) and cortisol in the human. For this purpose somatostatin (4.1 micrograms/min for 120 min or oxytocin (0.4 micrograms/min for 120 min) was infused into two different groups of seven healthy subjects; 30 min after the start of the infusion, placebo or insulin (0.1 IU/kg body weight, B.W.) was injected on two different days. In a third experimental step, an insulin tolerance test was performed during saline infusion to evaluate stress-related effects on the different hormonal secretions under basal conditions. Plasma levels of beta-END, beta-LPH and cortisol were measured by radioimmunoassay. Extraction and chromatographic procedures preceded the assay for beta-END and beta-LPH. Neither somatostatin nor oxytocin significantly modified basal plasma levels of beta-END, beta-LPH and cortisol. However these treatments blunted the rise of the three hormones seen at 45 and 60 min during insulin-induced hypoglycaemia (P less than 0.01). These results indicate that somatostatin and oxytocin may influence the beta-END, beta-LPH and cortisol increase induced by stress in humans, without affecting their basal secretion.

Topics: Adult; beta-Endorphin; beta-Lipotropin; Depression, Chemical; Endorphins; Female; Humans; Hydrocortisone; Hypoglycemia; Male; Oxytocin; Somatostatin

To assess the effect of cholinergic blockade on the ACTH, beta-endorphin and cortisol responses to insulin-induced hypoglycaemia, six healthy male volunteers each underwent two insulin tolerance tests in random order, separated by at least 1 week with and without atropine. ACTH levels were significantly greater at +45 min (mean +/- SEM, 223 +/- 21 pg/ml vs 148 +/- 15 pg/ml, P less than 0.01) and at +120 min (54 +/- 11 pg/ml vs 29 +/- 10 pg/ml, P less than 0.05). beta-endorphin levels were significantly greater at +30 min (170 +/- 45 pg/ml vs 96 +/- 32 pg/ml, P less than 0.05) and at +105 min (81 +/- 14 pg/ml vs 54 +/- 7 pg/ml, P less than 0.01). Cholinergic blockade had no effect on plasma glucose or cortisol concentrations. This study demonstrates that cholinergic blockade with atropine facilitates the ACTH and beta-endorphin responses to insulin-induced hypoglycaemia without altering the cortisol responses.

Topics: Adrenocorticotropic Hormone; Adult; Atropine; beta-Endorphin; Endorphins; Humans; Hydrocortisone; Hypoglycemia; Insulin; Male

Evidence that gamma-aminobutyric acid (GABA) and benzodiazepine receptors play a role in the inhibition of ACTH-cortisol secretion in humans has until now been drawn only from data indicating that sodium valproate, a GABA mimetic, and diazepam, a benzodiazepine, decrease hypothalamus-pituitary-adrenal (HPA) axis secretion in patients affected by pathological hypersecretion of the axis. Therefore, the present study investigated the effects, in the same healthy subjects, of sodium valproate or diazepam, on both basal and stress-stimulated concentrations of beta-endorphin (beta-EP), beta-lipotropin (beta-LPH) and cortisol. A single maximal dose of sodium valproate (400 mg) or diazepam (10 mg) did not significantly modify basal concentrations of beta-EP, beta-LPH and cortisol. On the other hand, in the same subjects, pretreatment with sodium valproate (20 mg X 3) or diazepam (10 mg X 2) blocked the increases in these hormones produced by hypoglycemic stress in all patients tested (p less than 0.01 vs. placebo at 45, 60 and 90 min after insulin injection), without affecting the decrease in blood glucose levels. The present data show that sodium valproate and diazepam inhibit stress-induced beta-EP, beta-LPH and cortisol secretion in humans, suggesting that endogenous GABA and benzodiazepine receptors participate in physiological mechanisms regulating the activity of the HPA axis.

Topics: Adult; beta-Endorphin; beta-Lipotropin; Diazepam; Endorphins; Female; Humans; Hydrocortisone; Hypoglycemia; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Receptors, GABA-A; Stress, Physiological; Valproic Acid

Repeated hypoglycemia is associated with hypoglycemia-associated autonomic failure (HAAF), a syndrome of defective counterregulation.. HAAF increases the risk of severe hypoglycemia in diabetes, although its mechanism remains unresolved. Because beta-endorphin influences the autonomic response to hypoglycemia via opioid receptor activation, we hypothesized that it is also involved in the pathogenesis of HAAF.. We asked whether opioid receptor blockade during antecedent hypoglycemia (60 mg/dl) on d 1 would prevent development of HAAF on d 2 in eight nondiabetic subjects (five males, 3 females; age, 28 +/- 3.5 yr; body mass index, 24.2 +/- 2.1 kg/m(2)). On four occasions, d 1 was: 1) two 90-min hypoglycemic clamps (N-); 2) two 90-min hypoglycemic clamps plus naloxone (N+); 3) two euglycemic 90-min clamps (C); or 4) two euglycemic 90-min clamps plus naloxone (C+).. Day 1 hypoglycemia caused marked deterioration of d 2 hormonal responses to hypoglycemia, consistent with HAAF-i.e. decreased plasma epinephrine, norepinephrine, and glucagon compared to control (C) (374 +/- 71 vs. 810 +/- 94, 307 +/- 65 vs. 686 +/- 98, and 71 +/- 9 vs. 93 +/- 4 pg/ml, respectively, P < 0.01), as well as in endogenous glucose production (24 vs. 163%; P < 0.01). In contrast, naloxone on d 1 completely prevented the defective counterregulatory responses; epinephrine, norepinephrine, and glucagon (852 +/- 82, 769 +/- 77, and 98 +/- 7 pg/ml) and endogenous glucose production recovery (167%) were identical to those after d 1 euglycemia (P < NS for all). Infusion of naloxone alone during euglycemia on d 1 (C+) had no effect on d 2 responses.. These data suggest that the opioid signaling system is a promising target for further studies to prevent HAAF.

Topics: Adult; Autonomic Nervous System Diseases; beta-Endorphin; Blood Glucose; C-Peptide; Epinephrine; Female; Glucagon; Gluconeogenesis; Humans; Hypoglycemia; Insulin; Male; Naloxone; Narcotic Antagonists; Norepinephrine; Receptors, Opioid; Syndrome

Although serotonin, serotonin uptake inhibitors and serotonin precursors (including tryptophan or 5-hydroxytryptophan) are known to have hypoglycemic action in rodents or human, it is not clear whether serotonin has hypoglycemic effect in streptozotocin-induced diabetic rats (STZ-diabetic rats). The aim of this study was to investigate the action of serotonin in regulating the plasma glucose STZ-diabetic rats. Plasma glucose, insulin, beta-endorphin and adrenaline were assessed after intraperitoneal administration of serotonin. Serotonin produced hypoglycemic effects without altering plasma insulin and adrenaline levels but increasing beta-endorphin level in STZ-diabetic rats. The glycogen content in soleus muscle was increased at 90 min after application of serotonin (0.3 mg/kg) in STZ-diabetic rats. Dihydroergotamine (non-selective 5-HT receptor blocker) and pimozide (5-HT(7) receptor blocker) abolished the hypoglycemic effect of serotonin in STZ-diabetic rats. Serotonin-induced hypoglycemic effect in association with the increase of beta-endorphin release was abolished in bilaterally adrenalectomized STZ-diabetic rats. In isolated adrenal gland of STZ-diabetic rats, the increase of beta-endorphin secretion in response to serotonin was reduced by either dihydroergotamine or pimozide. Pretreatment with naloxone (1.0 mg/kg, i.p.) prevented serotonin-induced plasma glucose lowering effect in STZ-diabetic rats. The results demonstrated that serotonin may activate 5-HT(7) receptor on rat adrenal gland to enhance of beta-endorphin secretion, which then stimulates the opioid receptor to increase peripheral glucose utilization, resulting in decreased plasma glucose levels in STZ-diabetic rats.

Topics: Adrenal Glands; Animals; beta-Endorphin; Blood Glucose; Diabetes Mellitus, Experimental; Epinephrine; Glycogen; Hypoglycemia; Hypoglycemic Agents; Male; Muscle, Skeletal; Naloxone; Narcotic Antagonists; Rats; Rats, Wistar; Serotonin; Serotonin Antagonists; Streptozocin

In our previous studies, an insulin-dependent hypoglycemic effect produced by electroacupuncture (EA) was shown to be mediated by endogenous opioid peptides (EOP). In the present study, we applied 2 Hz EA to both zusanli acupoints (ST36) in the test group for 30 min, and to a nonacupoint area in the control group for 30 min to compare the acupoint specific character in the hypoglycemic effect of EA. Assays of plasma beta-endorphin and insulin levels were performed by ELISA kits. The insulin-dependent mechanism of the hypoglycemic effect was also investigated in streptozotocin (STZ)-induced diabetic rats. The mediation of EOP and the role of mu-opioid receptor were examined by naloxone and mu-opioid receptor knockout mice (MOR-KOM). The serotonin depletion was carried out by injecting (i.p.) p-chlorophenylalanine (PCPA); two low doses of serotonin were also injected (i.v.) to analyze the direct effect on plasma glucose levels. The hypoglycemic effect of EA was much greater in rats stimulated at ST36 than in rats receiving the same stimulation at the nonacupoint area. The plasma levels of insulin and beta-endorphin were also significantly elevated after stimulation of both zusanli acupoints, but remained unchanged following stimulation at the nonacupoint area. There was no sharp hypoglycemic response to 2 Hz EA at zusanli acupoint of STZ-induced diabetic rats. However, the hypoglycemic effect of this EA was not totally blocked by the sufficient dose of naloxone (1 mg/kg, i.v.). Additionally, 2 Hz EA at ST36 also showed a sharp decrease in plasma glucose levels of MOR-KOM. Pretreatment with PCPA did not reproduce hypoglycemic response to 2 Hz EA in naloxone-treated rats and MOR-KOM mice. Furthermore, injection of serotonin decreased the plasma glucose levels significantly. Therefore, we suggest that serotonin also involved in the hypoglycemic action of 2 Hz EA at both zusanli acupoints of normal rats.

Topics: Acupuncture Points; Analysis of Variance; Animals; beta-Endorphin; Blood Glucose; Drug Interactions; Electroacupuncture; Fasting; Fenclonine; Hypoglycemia; Insulin; Male; Mice; Mice, Knockout; Naloxone; Narcotic Antagonists; Rats; Receptors, Opioid, mu; Serotonin; Serotonin Antagonists; Streptozocin

We found that electroacupuncture (EA) at the Zhongwan acupoint released beta-endorphin to induce an insulin-dependent hypoglycemia in rats. The present study investigated the source of beta-endorphin. EA at 2 Hz for 30 min in rats decreased plasma glucose that could be abolished by naloxone. A similar effect of EA was also observed in wild-type mice but disappeared in mu-opioid receptor knockout mice. Mediation of the mu(1)-opioid receptor is considered from the blockade of response to EA by naloxonazine in rats. Otherwise, adrenalectomy abolished not only the hypoglycemic response to EA in rat and mouse but also the increase of plasma beta-endorphin and insulin by EA in rats. In conclusion, the increase of plasma beta-endorphin by EA at 2 Hz is mainly from the adrenal gland.

Topics: Acupuncture Points; Adrenal Glands; Adrenalectomy; Animals; beta-Endorphin; Blood Glucose; Electroacupuncture; Hypoglycemia; Insulin; Male; Mice; Mice, Knockout; Naloxone; Narcotic Antagonists; Rats; Rats, Wistar; Receptors, Opioid, mu

Acupuncture at the Zhongwan acupoint has been widely used in traditional Chinese medicine to relieve symptoms of diabetes mellitus. Our study investigated the effect on plasma glucose of electroacupuncture applied at the Zhongwan acupoint in rat diabetic models. Plasma concentrations of insulin, glucagon and beta-endorphin- were also determined using radioimmunoassay. A decrease in plasma glucose was observed in rats after electroacupuncture (15 Hz, 10 mA) for 30 min at the Zhongwan acupoint. This was observed in normal rats and rat models with Type II (non-insulin-dependent) diabetes mellitus. No significant effect on plasma glucose was observed in rat models with Type I (insulin-dependent) diabetes mellitus: neither the streptozotocin (STZ)-induced diabetic rats nor the genetic (BB/W) rats. Further, the hypoglycaemic action of electroacupuncture stimulation disappeared in rats with insulin-resistance induced by an injection of human long-acting insulin repeated daily to cause the loss of tolbutamide-induced hypoglycaemia. An insulin-related action can thus be hypothesised. This hypothesis is supported by an increase in plasma insulin-like immunoreactivity after electroacupuncture stimulation in normal rats. Participation of glucagon was ruled out because there was no change in plasma glucagon-like immunoreactivity resulting from electroacupuncture stimulation. In addition to an increase in plasma beta-endorphin-like immunoreactivity, the plasma glucose lowering action of electroacupuncture stimulation at Zhongwan acupoint was abolished by naloxone in a sufficient dose to block opioid receptors. Thus we suggest that electroacupuncture stimulation at the Zhongwan acupoint induces secretion of endogenous beta-endorphin which reduces plasma glucose concentration in an insulin-dependent manner.

Topics: Acupuncture Points; Animals; beta-Endorphin; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Electroacupuncture; Glucagon; Hypoglycemia; Insulin; Insulin Resistance; Male; Naloxone; Narcotic Antagonists; Rats; Rats, Wistar; Tolbutamide

Several pituitary hormones, including corticotropin (ACTH), growth hormone (GH), prolactin, and beta-endorphin (but not thyrotropin, follicle-stimulating hormone, or luteinizing hormone), are released in response to hypoglycemia in normal subjects. In patients with insulin-dependent diabetes mellitus (IDDM), the degree of glycemic control is known to alter ACTH and GH responses to hypoglycemia. The current study was performed to examine the effect of glycemic control on prolactin and beta-endorphin responses to hypoglycemia in subjects with IDDM. We performed 3-hour stopped hypoglycemic-hyperinsulinemic clamp studies (12 pmol/kg/min) during which plasma glucose was decreased from 5.0 mmol/L to 2.2 mmol/L in steps of 0.6 mmol/L every 30 minutes in 20 subjects with uncomplicated IDDM (12 males and eight females; age, 26 +/- 2 years; IDDM duration, 10 +/- 1 years; body mass index, 23.6 +/- 0.6 kg/m2) and 10 healthy subjects (five males and five females aged 30 +/- 1 years). The 10 diabetic subjects in good glycemic control (mean hemoglobin A1 [HbA1], 7.5% +/- 0.3%; normal range, 5.4% to 7.4%) were compared with the 10 poorly controlled patients (mean HbA1, 12.6% +/- 0.5%; P < .001 v well-controlled diabetic group). During hypoglycemia, prolactin levels in the well-controlled diabetic group did not change (7 +/- 1 microgram/L at plasma glucose 5.0 mmol/L to 9 +/- 2 micrograms/L at plasma glucose 2.2 mmol/L), whereas prolactin levels increased markedly in the poorly controlled diabetic group (7 +/- 2 micrograms/L to 44 +/- 17 micrograms/L) and healthy volunteers (12 +/- 2 micrograms/L to 60 +/- 19 micrograms/L, P < .05 between IDDM groups). The plasma glucose threshold required for stimulation of prolactin secretion was 2.2 +/- 0.1 mmol/L in well-controlled IDDM, 3.0 +/- 0.4 mmol/L in poorly controlled IDDM, and 2.4 +/- 0.1 mmol/L in healthy subjects (P < .05 between IDDM groups). Responses in males and females were similar. The increase in beta-endorphin levels was also attenuated in well-controlled IDDM patients (4 +/- 1 pmol/L at plasma glucose 5.0 mmol/L to 11 +/- 4 pmol/L at plasma glucose 2.2 mmol/L) versus poorly controlled IDDM patients (5 +/- 1 pmol/L to 26 +/- 7 pmol/L) and healthy subjects (8 +/- 1 pmol/L to 56 +/- 13 pmol/L). The plasma glucose threshold required for stimulation of beta-endorphin release was again lower in well-controlled IDDM versus poorly controlled IDDM patients (2.2 +/- 0.1 v 3.0 +/- 0.3 mmol/L) and healthy subjects (2.5 +/- 0.

Topics: Adult; beta-Endorphin; Blood Glucose; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Insulin; Male; Prolactin; Sex Factors

In patients with chronic renal failure (CRF) an elevated serum beta-endorphin (BE) level and lack of a twenty-four-hour BE-secretory pattern were found. BE and other opioid peptides participate significantly in the development of the uremic syndrome and its complications. On the other hand hemodialytic treatment is an important factor influencing the concentration of most hormones. In healthy subjects insulin-induced hypoglycemia as well as exogenous corticotropin releasing hormone (CRH) produce a rise in serum BE since BE, beta-lipotropin and ACTH come from the common precursor proopiomelanocortin (POMC). This paper intended to evaluate the curve of serum BE concentration during such a test in uremic patients on hemodialytic treatment. 13 patients with CRF hemodialysed 4 to 38 months (mean: 17 months) and 14 healthy subjects were examined. In each of them crystalline insulin (0.1 units/kg of body mass) was given intravenously and blood samples were collected every 30 minutes. BE concentration was measured by radioimmunoassay without previous chromatographic separation. The test was performed after an overnight rest in the morning in persons staying at the recumbent position. An adequate hypoglycemia was obtained in every subject. Basal serum BE concentration was significantly higher in patients with CRF than in healthy subjects and correlated positively with duration of hemodialytic treatment. After 60 min. from insulin injection in both groups the peak BE level was observed whereas after 120 min. in returned to the initial values. The curve of BE concentration in patients with CRF ran on a significantly higher level than in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; beta-Endorphin; Female; Humans; Hypoglycemia; Insulin; Kidney Failure, Chronic; Male; Middle Aged; Reference Values; Renal Dialysis

We have previously found that histamine (HA) is involved in the mediation of restraint- and ether stress-induced release of the POMC-derived peptides ACTH and beta-endorphin (beta-END). In the present study we investigated the possible involvement of hypothalamic histaminergic neurons in the mediation of insulin/hypoglycemia-induced release of ACTH and beta-END in conscious male rats. To do so, hypoglycemia stress was performed during 1) inhibition of HA synthesis, 2) activation of inhibitory presynaptic HA H3-auto-receptors, or 3) blockade of postsynaptic HA H1- or H2-receptors. Hypoglycemia (plasma glucose, 2.2 +/- 0.3 nmol) induced by insulin (3 IU/kg, ip) caused a 3- to 5-fold increase in the plasma concentrations of ACTH and beta-END. A negative exponential correlation was found between the plasma glucose concentration and the ACTH and beta-END levels. Pretreatment of the animals with the HA synthesis inhibitor alpha-fluoromethylhistidine (1.0 mumol) intracerebroventricularly (icv) in a lateral ventricle, inhibited the ACTH and beta-END responses to insulin/hypoglycemia by 60%. When administered ip (100 mumol/kg), the synthesis inhibitor decreased the beta-END response 50%, but did not affect ACTH secretion significantly. Pretreatment of the rats with the H3-receptor agonist R(alpha)methylhistamine (50 mumol/kg, ip, twice) inhibited the secretory responses of ACTH and beta-END to insulin/hypoglycemia by 60-80%. This inhibitory effect of R(alpha)methylhistamine was reversed by prior administration of the specific H3-receptor antagonist thioperamide. Administration of the H1-antagonists mepyramine and cetirizine dose-dependently inhibited the ACTH and beta-END responses to insulin/hypoglycemia, with the highest dose (mepyramine, 350 nmol, icv; cetirizine, 40 mumol/kg, ip) inhibiting the response by 80-100%. The H1-antagonist SKF-93944 (226 nmol, icv) inhibited the ACTH response, but had no effect on the beta-END response. Administration of the H2-antagonists cimetidine (400 nmol, icv) and ranitidine (400 nmol, icv) inhibited the ACTH and beta-END responses to insulin/hypoglycemia by 50-80%. We conclude that histaminergic neurons are involved in the mediation of the insulin/hypoglycemia-induced release of ACTH and beta-END and that the effect is mediated via activation of primarily postsynaptic H1-receptors and, to a lesser extent, H2-receptors.

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Cetirizine; Cimetidine; Histamine; Histamine Agonists; Histamine Antagonists; Hypoglycemia; Hypothalamus; Insulin; Male; Methylhistamines; Neurons; Pyrilamine; Pyrimidinones; Rats; Rats, Wistar

The stress-induced release of anterior pituitary hormones and changes in hypothalamic content of histamine (HA) and its metabolite tele-methylHA (t-meHA) were studied in male rats during inhibition of HA synthesis or activation or blockade of HA H3 receptors. Pretreatment with the HA synthesis inhibitor alpha-fluoromethylhistidine (alpha-FMH; 200 micrograms intracerebroventricularly (icv) at -120 min) or the specific H3 receptor agonist R(alpha)methylhistamine (RmHA; 10 mg/kg intraperitoneally (ip) at -180 and -60 min) inhibited by 30-80% the responses of prolactin (PRL), corticotropin (ACTH) and beta-endorphin (beta-END) immunoreactivity to 1, 2.5 or 5 min of restraint stress (p < 0.05-0.01), but had no effect on basal secretion of the hormones. The inhibitory effect of the H3 receptor agonist RmHA (10 mg/kg x 2) on the hormone response to 5 min of restraint stress was prevented by simultaneous ip administration of the H3 receptor antagonist thioperamide. alpha-FMH reduced the hypothalamic content of HA 60% and that of t-meHA 30%, while RmHA had no effect on the HA content. Restraint stress for 5 min did not affect the HA and t-meHA contents, which may be due to the short duration of stress exposure. Pretreatment with the H3 receptor antagonist thioperamide (5 or 10 mg/kg ip at -120 min) had no effect on basal or restraint stress-induced release of PRL, ACTH or beta-END, although the compound increased the hypothalamic content of t-meHA 2-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Histamine; Histamine Antagonists; Hypoglycemia; Hypothalamus; Insulin; Kinetics; Male; Methylhistamines; Methylhistidines; Piperidines; Pituitary Hormones, Anterior; Prolactin; Rats; Rats, Wistar; Receptors, Histamine; Receptors, Histamine H3; Restraint, Physical; Stress, Physiological

In the present study, we investigated the coordinate kinetic response of the corticotropic axis to the acute metabolic stress of hypoglycemia by applying deconvolution analysis to adrenocorticotropin (ACTH), beta-endorphin and cortisol concentration-time series generated in seven normal men after intravenous administration of insulin. Hypoglycemic stress resulted in a 22-fold increase in the mean plasma concentration of ACTH to a maximum of 77 +/- 15 pmol/l, in conjunction with a 7.5-fold increase in the mean plasma beta-endorphin concentration, the maximal value of which was 96 +/- 11 pmol/l. Plasma cortisol concentrations increased by 2.6-fold with a mean value of 734 +/- 14 nmol/l. Maximal plasma ACTH and beta-endorphin concentrations were preceded by discrete secretory bursts with peak amplitudes of 10.5 +/- 2.7 and 10.6 +/- 2.0 pmol.l-1.min-1 (20-fold and ninefold increases compared to control), respectively. The mass of ACTH released was 114 +/- 20 pmol/l (3.4-fold increase), which corresponds to a total amount of 1.25 micrograms (50% of daily production and 0.5% of reported pituitary stores), assuming a distribution volume of 40 ml/kg. A total amount of 4.4 +/- 0.7 mg of cortisol was released after insulin-induced hypoglycemia, based on a mean cortisol secretory mass of 1088 +/- 137 nmol/l and a presumed 11.3-1 volume of distribution. Deconvolution-based estimates of the endogenous half-lives of ACTH, beta-endorphin and cortisol were 17 +/- 0.6, 22 +/- 1.7 and 65 +/- 5.3 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Blood Glucose; Half-Life; Humans; Hydrocortisone; Hypoglycemia; Hypothalamo-Hypophyseal System; Insulin; Male; Middle Aged; Pituitary-Adrenal System; Time Factors

beta-endorphin (BE) and other opioid peptides participate significantly in the development of the uremic syndrome. In patients with chronic renal failure (CRF) an elevated serum BE level and lack of a twenty-four-hour BE-secretory pattern were found. In 14 patients with CRF on conservative treatment with serum creatinine above 500 mumol/l and in 14 healthy subjects serum BE was evaluated after intravenous insulin injection. An adequate hypoglycemia was obtained in every subject. Basel serum BE concentration was significantly higher in patients with CRF than in healthy subjects and correlation positively with creatinine. After 60 min. from insulin injection in both groups the peak BE level was observed here after 120 min. it returned to the initial values. The curve of BE concentration in patients with CRF ran significantly higher than in healthy subjects. A total secretory answer of the pituitary measured by the area over basel value of BE was similar in both groups. It seems that BE secretion by the corticotropic cells of the pituitary is unchanged in patients with CRF. Impaired BE elimination by the kidneys is probably responsible for hyper-beta-endorphin levels in those patients.

Topics: Adult; beta-Endorphin; Female; Humans; Hypoglycemia; Insulin; Kidney Failure, Chronic; Male; Middle Aged

Endogenous opioid peptides have a role in the regulation of the hypothalamic-pituitary-adrenal axis. Recently, beta-endorphin (EP) has been thought to inhibit CRF release in vivo and in vitro. In the present study we examined the effects of central administration of EP on ACTH secretion and gene expression of both CRF in the hypothalamus and POMC in the anterior pituitary gland (AP) during basal and insulin-induced hypoglycemia in pentobarbital-anesthetized rats. Administration of EP in the lateral ventricle decreased basal CRF levels in the median eminence and inhibited basal and hypoglycemia-induced ACTH secretion in a dose-dependent manner. Hypoglycemia-induced POMC mRNA levels in the AP and CRF mRNA levels in the hypothalamus were also dose-dependently inhibited by the administration of EP. The inhibitory effect of EP was reversed by naloxone. These results suggest that 1) central administration of EP acts through the opioid receptor to inhibit hypoglycemia-induced CRF gene expression in the hypothalamus and CRF release, which results in a decrease in ACTH secretion and POMC mRNA levels in the AP; and 2) the active site of EP is the CRF neuron in the paraventricular nucleus.

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Blotting, Northern; Corticotropin-Releasing Hormone; Gene Expression; Hypoglycemia; Hypothalamus; Injections, Intraventricular; Male; Pituitary Gland, Anterior; Pro-Opiomelanocortin; Radioimmunoassay; Rats; Rats, Inbred Strains; RNA, Messenger

Pancreatic tissue from 3 cases of hyperinsulinemic hypoglycemia was examined using histochemical and immunoperoxidase staining techniques. The insular lesions present were adenomatosis and insulin-producing islet-cell adenomata. The great majority of the islet parenchymal cells in these lesions were reactive with antibodies to pro-insulin, C-peptide, and insulin. A variable number of islet cells was found to react with beta-endorphin antiserum in all 3 cases, while the reaction with antiserum against the neural tissue marker antigen, S-100, was restricted to the cases with islet-cell adenoma. Argyrophil parenchymal cells were present in focal adenomatosis but almost absent in insulomata. These results suggest that various lesions of the endocrine pancreas causing hypoglycemia can be distinguished by means of specific histo- and immunocytochemical methods because of differences in the distribution of characteristic cellular antigens.

Topics: Adenoma; Adenoma, Islet Cell; Adolescent; Adult; beta-Endorphin; Child; Child, Preschool; Female; Humans; Hypoglycemia; Immunoenzyme Techniques; Immunohistochemistry; Infant; Insulin; Insulin Secretion; Male; Middle Aged; Pancreatic Neoplasms; Radioimmunoassay

Recently, our laboratory has reported that central administration of beta-endorphin to rat pups decreases hepatic and renal ornithine decarboxylase activity, a sensitive biochemical index of tissue metabolic activity. Since these organs are the major sites of insulin catabolism, it seemed possible that the plasma levels of this hormone could be altered by changes in central nervous system (CNS) beta-endorphin levels. In the current study we tested this hypothesis by administering beta-endorphin to rat pups intracisternally (ic), followed by insulin sc, and then analyzing for plasma levels of insulin and glucose at various times after the second injection. We found that the apparent biological half-life of administered insulin markedly increased in 6-day-old rats pretreated with beta-endorphin ic. Similarly, this neuropeptide prolonged the half-life of endogenous insulin, as indicated by a small but significant increase in the plasma levels of this hormone in animals given only beta-endorphin. As expected, hypoglycemia in rats injected with beta-endorphin and insulin was more pronounced than in animals given insulin alone. Naloxone administered ic reversed both actions of beta-endorphin, indicating the involvement of opioid receptors in the response. beta-Endorphin also altered insulin and glucose plasma levels in 2-, 10-, and 18-day-old rats, but there were no effects in 30-day-old animals at any of the doses used in these studies. Peripheral administration of beta-endorphin had no effect, indicating that CNS beta-endorphin's influences on insulin and glucose metabolism occur through brain-based mechanisms. The results from these studies suggest that CNS beta-endorphin may be an important modulator of insulin and glucose metabolism in preweanling rats. In as much as insulin is a major regulator of somatic growth, our findings further suggest that CNS beta-endorphin may have a major role in the control of growth during early postnatal development by influencing insulin homeostasis.

Topics: Animals; Animals, Suckling; beta-Endorphin; Blood Glucose; Central Nervous System; Dose-Response Relationship, Drug; Hypoglycemia; Insulin; Naloxone; Rats; Rats, Inbred Strains

The present study was designed to examine the role played by beta-endorphin in the physiological response to the stress of insulin-induced hypoglycemia. Three groups (n = 5, each) of conscious overnight-fasted dogs, chronically fitted with catheters in the femoral artery and in the third ventricle were used for these studies. Each experiment consisted of an 80-min equilibration period (0-80 min), a 40-min basal period (80-120 min), and a 180-min (120-300 min) experimental period. One group received a 220-min intracerebroventricular (icv) infusion of naloxone (0.2 mg/h) beginning at t = 80 min. The second group received a 3-h intravenous infusion of insulin at 5.0 mU.kg-1.min-1 beginning at t = 120 min. The third group received naloxone at t = 80 min and insulin beginning at t = 120 min, and both were continued throughout the experimental period. The studies show that insulin-induced hypoglycemia was associated with a rise in plasma cortisol, beta-endorphin, epinephrine, norepinephrine, and glucagon. Pretreatment with naloxone diminished the rises in plasma beta-endorphin, epinephrine, and norepinephrine without affecting the responses of plasma glucagon and cortisol. Although the levels of hypoglycemia achieved in the two groups were identical, glucose rates of appearance into and disappearance from the plasma compartment were higher in the group pretreated with icv naloxone (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; beta-Endorphin; Blood Glucose; Dogs; Epinephrine; Glucagon; Glucose; Homeostasis; Hydrocortisone; Hypoglycemia; Insulin; Naloxone; Norepinephrine

Studies were undertaken to characterize the secretion of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) into the hypophysial-portal circulation of the conscious sheep. In addition, we examined the temporal relationship between the secretion of these two hypothalamic peptides and the secretion of three pro-opiomelanocortin peptides--adrenocorticotropic hormone (ACTH), ir-beta-endorphin, and ir-alpha-melanocyte-stimulating hormone--and cortisol and determined the effects of an audiovisual emotional stimulus and insulin-induced hypoglycemia on the entire hypothalamic-pituitary-adrenal axis. In the basal state, the secretion of CRF, AVP, the three pro-opiomelanocortin peptides, and cortisol was pulsatile in nature, and three CRF and AVP pulse patterns were observed: a concordant increase in CRF and AVP, an isolated rise in CRF, and an isolated increase in AVP. In 4 of the 5 animals, a 3-min audiovisual stress (barking dog) rapidly increased the plasma levels of all the measured substances, although the magnitude and duration of the effect differed markedly between the animals. Insulin-induced hypoglycemia markedly increased AVP and, to a lesser extent, CRF concentrations in portal plasma and thereby altered the CRF:AVP molar ratio. Although pituitary-adrenal activation was closely correlated with the increased hypothalamic activity, a strict 1:1 concordance between CRF/AVP secretion and ACTH secretion was not seen. The anesthetic ketamine selectively increased portal AVP concentrations to levels which exceeded those attained during hypoglycemia and rapidly activated the pituitary-adrenal axis. We conclude the following: (1) CRF and AVP are secreted by the hypothalamus in a pulsatile fashion; (2) ACTH secretion can be stimulated by increases in either CRF or AVP; (3) the absence of a strict 1:1 concordance between hypothalamic CRF/AVP release and pituitary ACTH secretion during stress may be partly due to the release of additional hypothalamic ACTH secretagogues; (4) the ability of both audiovisual stimuli and insulin-induced hypoglycemia to augment CRF and AVP secretion indicates that the paraventricular hypothalamus may be activated by a variety of neural inputs, and (5) the marked alteration of the CRF:AVP molar ratio during stress suggests that AVP may be an important ACTH secretagogue in vivo in the sheep.

Topics: Adrenocorticotropic Hormone; alpha-MSH; Animals; Arginine Vasopressin; beta-Endorphin; Corticotropin-Releasing Hormone; Female; Hydrocortisone; Hypoglycemia; Hypothalamus; Pituitary Gland; Radioimmunoassay; Sheep; Stress, Physiological

This study was designed to assess effects of insulin-induced hypoglycemia on plasma and cerebrospinal fluid (CSF) levels of immunoreactive (ir) beta-endorphins, adrenocorticotropin (ACTH), cortisol, norepinephrine, insulin, and glucose in the conscious, overnight fasted dog. Dogs received either an intravenous infusion of saline or insulin (5 mU/kg/min) for 3 h. Infusion of saline alone in conjunction with acute sampling of CSF caused no measurable perturbations of glucose homeostasis. Insulin infusion caused a 60% drop in both plasma and CSF glucose. Plasma levels of ir-beta-endorphins, ACTH and cortisol rose markedly. CSF levels of ir-beta-endorphins and ACTH also increased. While the magnitude of the increase was smaller than that in the plasma, it was greater than would be expected if crossover of the peptides from the plasma were the sole source of the increase. Hypoglycemia also induced elevations in CSF cortisol and insulin. In addition, there was a 45% decrease in CSF norepinephrine in spite of large elevations of norepinephrine in the plasma. We conclude that hypoglycemia is associated with marked changes in central as well as peripheral levels of neuroendocrine factors. The importance of these changes in mediating acute and long-term responses to hypoglycemia remains to be established.

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Blood Glucose; Dogs; Glucose; Hormones; Hydrocortisone; Hypoglycemia; Insulin; Kinetics; Norepinephrine; Reference Values

Acute insulin-induced hypoglycaemia in humans provokes autonomic neural activation and counterregulatory hormonal secretion mediated in part via hypothalamic stimulation. Many patients with Type 1 (insulin-dependent) diabetes have acquired deficiencies of counterregulatory hormonal release following hypoglycaemia. To study the integrity of the hypothalamic-pituitary and the sympatho-adrenal systems, the responses of pituitary hormones, beta-endorphin, glucagon and adrenaline to acute insulin-induced hypoglycaemia (0.2 units/kg) were examined in 16 patients with Type 1 diabetes who did not have autonomic neuropathy. To examine the effect of duration of diabetes these patients were subdivided into two groups (Group 1: 8 patients less than 5 years duration; Group 2: 8 patients greater than 15 years duration) and were compared with 8 normal volunteers (Group 3). The severity and time of onset of hypoglycaemia were similar in all 3 groups, but mean blood glucose recovery was slower in the diabetic groups (p less than 0.01). The mean responses of glucagon, adrenaline, adrenocorticotrophic hormone, prolactin and beta-endorphin were similar in all 3 groups, but the mean responses of growth hormone were lower in both diabetic groups than in the normal group (p less than 0.05). The mean increments of glucagon and adrenaline in the diabetic groups were lower than the normal group, but these differences did not achieve significance; glucagon secretion was preserved in several diabetic patients irrespective of duration of disease. Various hormonal responses to hypoglycaemia were absent or diminished in individual diabetic patients, and multiple hormonal deficiencies could be implicated in delaying blood glucose recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; Blood Glucose; Diabetes Mellitus, Type 1; Epinephrine; Female; Glucagon; Growth Hormone; Hormones; Humans; Hypoglycemia; Hypothalamo-Hypophyseal System; Insulin; Male; Middle Aged; Prolactin; Reference Values

These studies were undertaken to characterize the secretion of adrenocorticotropin (ACTH), immunoreactive (ir) beta-endorphin (ir-beta-EP) and ir alpha-melanocyte-stimulating hormone (ir-alpha-MSH) from the surgically isolated ovine pituitary in response to an audiovisual stress (barking dog, 3 min) and insulin hypoglycemia. The studies were performed in 4 ovariectomized, hypothalamo-pituitary-disconnected (HPD) and 4 sham-HPD ewes bearing indwelling jugular venous catheters. Basal concentrations of the three pro-opiomelanocortin (POMC) peptides and plasma cortisol were significantly increased in the HPD animals. When the control ewes were exposed to the audiovisual stimulus, plasma ACTH, ir-beta-EP and ir-alpha-MSH levels were increased 2.5-, 10-, and 5-fold 1 min after the stress; plasma cortisol attained maximal values at 5 min. In contrast, plasma levels of the three POMC peptides were not significantly increased in the HPD animals, although a rise in plasma cortisol occurred. The administration of regular insulin (5 units/kg i.v.) to control ewes caused plasma ACTH, ir-beta-EP, and ir-alpha-MSH levels to increase 17-, 22-, and 67-fold at 50 min; plasma cortisol values were maximal at 60 min. In contrast, the elevated basal levels of POMC peptides in the HPD animals were not significantly increased by the hypoglycemia, but a significant elevation of plasma cortisol was seen. We conclude that: (1) the increase in ACTH in intact animals after an audiovisual emotional stress and hypoglycemia, and the abolition of this increase by HPD, indicates that both stimuli, each acting through distinct neuroanatomical pathways, increase the net corticotropin-releasing activity of the hypothalamus; (2) the rise in plasma cortisol in HPD animals after stress suggests that peripheral humoral factors may release additional small amounts of ACTH from the anterior pituitary, and (3) the finding of increased basal ACTH levels after HPD suggests that POMC peptide synthesis and secretion by the anterior pituitary is tonically regulated by an inhibitory factor of hypothalamic origin.

Topics: Adrenocorticotropic Hormone; Animals; Audiometry, Evoked Response; beta-Endorphin; Hypoglycemia; Hypothalamo-Hypophyseal System; Hypothalamus; Insulin; Melanocyte-Stimulating Hormones; Photic Stimulation; Pituitary Gland; Pituitary-Adrenal System; Sheep; Stress, Physiological

The placenta has been shown to contain ACTH and beta-endorphin but the roles of these peptides are unknown. To investigate whether they are released into the maternal circulation from the placenta in response to physiological stimuli the effects of hypoglycaemic stress were investigated. Plasma samples were collected from the femoral artery (FA) and uterovarian (UV) vein of nine pregnant sheep before and during hypoglycaemia induced by intravenous insulin (100U). Plasma concentrations of ovine beta-endorphin (o beta-EP) were measured by radioimmunoassay. Concentrations of o beta-EP rose in both vessels by 60 min after insulin. The peak concentrations of o beta-EP (pmol/l) were 122 +/- 29 (mean +/- SEM, n = 8) in the UV and 96 +/- 24 (n = 9) fmol/ml in the FA 60 min after insulin injection. There was no difference between the concentrations of o beta-EP in the vessels before insulin injection but at 60 and 120 min after insulin the concentrations of o beta-EP were significantly higher in the UV than FA (P less than 0.02, analysis of variance). This indicates that the pregnant uterus or placenta can respond to hypoglycaemia by secreting beta-EP into the maternal circulation. It is therefore possible that placental pro-opiomelanocortin (POMC) peptides may have a role in maternal endocrinology and metabolism.

Topics: Animals; beta-Endorphin; Female; Hypoglycemia; Insulin; Pregnancy; Pregnancy Complications; Sheep; Stress, Physiological; Time Factors

Topics: Adult; beta-Endorphin; Diabetes Mellitus, Type 2; Female; Glucagon; Growth Hormone; Humans; Hydrocortisone; Hypoglycemia; Insulin

Topics: Adult; beta-Endorphin; Female; Growth Hormone; Humans; Hydrocortisone; Hypoglycemia; Insulin; Obesity; Prolactin

A specific double antibody radioimmunoassay (RIA) for human beta-endorphin (beta-EP) using an antibody to synthetic beta h-endrophin was established. This antibody cross-reacted with beta-Lipotropin (beta-LPH) at 42 per cent on molar basis and allowed a usable range of 20 pg to 4 ng of beta-endorphin per ml in the assay. Comparing the efficiency of the conventional extraction procedures under various conditions using Corning glass, Vycor glass, QUSO G-32, silicic acid and controlled pore glass 75, the optimal result was obtained by Corning glass, with a recovery rate of more than 80 per cent. The most simple and rapid method with an extraction efficiency of more than 90 per cent was found to be the extraction by use of Sep-Pak C18 cartridges. The separation of beta-endorphin from beta-LPH was studied using Sephadex G-50, G-75, G-100 and Bio-Gel P-60 columns and different elution media. The use of a Sephadex G-50 column (0.9 X 55 cm) and elution with 0.1 N acetic acid-0.05 per cent HSA gave the best result. The reliability of the radioimmunoassay was shown under physiological and pathophysiological conditions.

Topics: beta-Endorphin; beta-Lipotropin; Chromatography, Gel; Endocrine System Diseases; Endorphins; Humans; Hypoglycemia; Radioimmunoassay

By use of the opiate antagonist naloxone, we have examined the hormonal and metabolic responses to opiate-receptor blockade under basal conditions and during insulin-induced hypoglycemia in normal dogs. Naloxone treatment had no measurable effect on glucose concentration, turnover, and norepinephrine levels, but stimulated plasma epinephrine, glucagon, and cortisol and inhibited insulin release. Insulin (7 mU X kg-1 X min-1) decreased plasma glucose to 42 +/- 4 mg/dl due to an initial decrease in glucose production and an increase in glucose disappearance. Glucose production then increased, and plasma glucose plateaued. After 50 min of insulin infusion, epinephrine levels increased 26-fold (P less than 0.05), norepinephrine and glucagon 3-fold (P less than 0.02), and cortisol 4-fold (P less than 0.01). Similarly, plasma beta-endorphin and adrenocorticotropin (ACTH) were elevated (6-fold, P less than 0.01, and 16-fold, P less than 0.05, respectively). When naloxone was given during insulin-induced hypoglycemia, there was earlier release of epinephrine, glucagon, beta-endorphin, ACTH, and cortisol as well as a greater release of glucagon (P less than 0.001) and cortisol (P less than 0.0001). This resulted in a greater increase in glucose production (P less than 0.01), thus lessening the insulin-induced hypoglycemic excursion. In conclusion, in the dog, endogenous opiates may play a small role in the regulation of basal insulin and glucagon release and can inhibit the pituitary-adrenal axis under basal conditions and during hypoglycemia. Thus increased glucose production in response to insulin-induced hypoglycemia is consistent with the excessive response of counterregulatory hormones during opiate-receptor blockade.

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Blood Glucose; Dogs; Endorphins; Glucagon; Hydrocortisone; Hypoglycemia; Insulin; Naloxone; Norepinephrine; Receptors, Opioid

The effect of insulin-induced hypoglycemic stress on the concentrations of immunoreactive beta-endorphin (ir beta-EP) in plasma and cerebrospinal fluid (CSF) was examined in conscious non-pregnant ewes in which the cisterna magna and a jugular vein had been previously catheterized. In control experiments, no significant changes were observed in plasma cortisol or ir beta-EP and CSF ir beta-EP concentrations. During hypoglycemia induced by intravenous injection of 20 units of insulin, plasma cortisol concentrations rose significantly, reaching a peak 1.5 h after injection. The changes in plasma ir beta-EP concentration were significantly different between hypoglycemic and normoglycemic sheep (analysis of variance, P = 0.0089). Following insulin injection, mean plasma ir beta-EP rose by 100% within 0.75 h, continued to rise six-fold over initial concentrations by 2.25 h, and remained elevated for 3.75 h. The CSF ir beta-EP concentrations following insulin injection were not significantly different from those observed in controls. These results suggest that if beta-endorphin mediated hypoglycemic stress-induced analgesia, its actions may be peripheral, not central.

Topics: Animals; beta-Endorphin; Blood Glucose; Endorphins; Female; Hydrocortisone; Hypoglycemia; Sheep; Sleep

The authors provide the data on the changes in the blood content of opioid neuropeptides in patients with Icenko-Cushing's disease treated with an antiserotonin drug peritol. The high content of beta-endorphine and beta-lipotropin in the patients' blood was one of the factors determining activation of the hypothalamus-pituitary-adrenal system. The treatment of patients with Icenko-Cushing's disease by peritol led to a decrease in the blood content of beta-endorphine and beta-lipotropin, promoting a clinical and laboratory remission in 60% of patients. Some patients treated with peritol did not develop a clinical remission. This indicates the necessity of acting on the metabolism of other monoamines involved in the modulation of the action of neuropeptides on the hypothalamus-pituitary system.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; beta-Lipotropin; Cushing Syndrome; Cyproheptadine; Drug Therapy, Combination; Endorphins; Female; Humans; Hydrocortisone; Hypoglycemia; Insulin; Male; Middle Aged; Mitotane

Topics: Anorexia Nervosa; beta-Endorphin; Endorphins; Female; Humans; Hypoglycemia; Male; Obesity; Physical Exertion

Topics: Animals; beta-Endorphin; Cats; Endorphins; Hypoglycemia; Insulin; Male; Radioimmunoassay