Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In humans there is a circadian rhythm of leptin concentrations in plasma with a minimum in the early morning and a maximum in the middle of the night. By taking blood samples from adult male rats every 3 hr for 24 hr, we determined that a circadian rhythm of plasma leptin concentrations also occurs in the rat with a peak at 0130h and a minimum at 0730h. To determine if this rhythm is controlled by nocturnally released hormones, we evaluated the effect of hormones known to be released at night in humans, some of which are also known to be released at night in rats. In humans, prolactin (PRL), growth hormone (GH), and melatonin are known to be released at night, and adrenocorticotropic hormone (ACTH) release is inhibited. In these experiments, conscious rats were injected intravenously with 0.5 ml diluent or the substance to be evaluated just after removal of the first blood sample (0.3 ml), and additional blood samples (0.3 ml) were drawn every 10 min thereafter for 2 hr. The injection of highly purified sheep PRL (500 microg) produced a rapid increase in plasma leptin that persisted for the duration of the experiment. Lower doses were ineffective. To determine the effect of blockade of PRL secretion on leptin secretion, alpha bromoergocryptine (1.5 mg), a dopamine-2-receptor agonist that rapidly inhibits PRL release, was injected. It produced a rapid decline in plasma leptin within 10 min, and the decline persisted for 120 min. The minimal effective dose of GH to lower plasma leptin was 1 mg/rat. Insulin-like growth factor (IGF-1) (10 microg), but not IGF-2 (10 microg), also significantly decreased plasma leptin. Melatonin, known to be nocturnally released in humans and rats, was injected at a dose of 1 mg/rat during daytime (1100h) or nighttime (2300h). It did not alter leptin release significantly. Dexamethasone (DEX), a potent glucocorticoid, was ineffective at a 0. 1-mg dose but produced a delayed, significant increase in leptin, manifest 100-120 min after injection of a 1 mg dose. Since glucocorticoids decrease at night in humans at the time of the maximum plasma concentrations of leptin, we hypothesize that this increase in leptin from a relatively high dose of DEX would mimic the response to the release of corticosterone following stress in the rat and that glucocorticoids are not responsible for the circadian rhythm of leptin concentration. Therefore, we conclude that an increase in PRL secretion during the night may be responsible, at least in part, for the nocturnal elevation of leptin concentrations observed in rats and humans.
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PMID:The possible role of prolactin in the circadian rhythm of leptin secretion in male rats. 1086 30

Hypothalamic melanocortins are among several neuropeptides strongly implicated in the control of food intake. Agonists for melanocortin 4 (MC-4) receptors such as alpha-melanocyte-stimulating hormone (alpha-MSH), a product of proopiomelanocortin (POMC), reduce food intake, whereas hypothalamic agouti-related protein (AgRP) is a MC-4 receptor antagonist that increases food intake. To investigate whether reduced melanocortin signaling contributes to hyperphagia induced by uncontrolled diabetes, male Sprague-Dawley rats were studied 7 days after administration of streptozotocin (STZ) or vehicle. In addition, we wished to determine the effect of diabetes on muscle uncoupling protein 3 (UCP-3), a potential regulator of muscle energy metabolism. STZ diabetic rats were markedly hyperglycemic (31.3 +/- 1.0 mmol/l; P < 0.005) compared with nondiabetic controls (9.3 +/- 0.2 mmol/l). Insulin treatment partially corrected the hyperglycemia (18.8 +/- 2.5 mol/l; P < 0.005). Plasma leptin was markedly reduced in STZ diabetic rats (0.4 +/- 0.1 ng/ml; P < 0.005) compared with controls (3.0 +/- 0.4 ng/ml), an effect that was also partially reversed by insulin treatment (1.8 +/- 0.3 ng/ml). Untreated diabetic rats were hyperphagic, consuming 40% more food (48 +/- 1 g/day; P < 0.005) than controls (34 +/- 1 g/day). Hyperphagia was prevented by insulin treatment (32 +/- 2 g/day). In untreated diabetic rats, hypothalamic POMC mRNA expression (measured by in situ hybridization) was reduced by 80% (P < 0.005), whereas AgRP mRNA levels were increased by 60% (P < 0.01), suggesting a marked decrease of hypothalamic melanocortin signaling. The change in POMC, but not in AgRP, mRNA levels was partially reversed by insulin treatment. By comparison, the effects of diabetes to increase hypothalamic neuropeptide Y (NPY) expression and to decrease corticotropin-releasing hormone (CRH) expression were normalized by insulin treatment, whereas the expression of mRNA encoding the long form of the leptin receptor in the arcuate nucleus was unaltered by diabetes or insulin treatment. UCP-3 mRNA expression in gastrocnemius muscle from diabetic rats was increased fourfold (P < 0.005), and the increase was prevented by insulin treatment. The effect of uncontrolled diabetes to decrease POMC, while increasing AgRP gene expression, suggests that reduced hypothalamic melanocortin signaling, along with increased NPY and decreased CRH signaling, could contribute to diabetic hyperphagia. These responses, in concert with increased muscle UCP-3 expression, may also contribute to the catabolic effects of uncontrolled diabetes on fuel metabolism in peripheral tissues.
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PMID:Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling protein 3 expression in rats. 1086 41

Given the tremendous number of neuropeptides, which are synthesized in the central nervous system, the brain can be viewed as one of the most prominent endocrine organs. Elucidation of the functions of these peptides is hampered by the facts that after intravenous administration access to brain receptors is prevented or impaired by the blood-brain barrier. Here, we provide evidence that intranasal administration can be a way to circumvent the blood-brain barrier. Selected experiments will be reported indicating that peptides after intranasal administration in humans can specifically alter a great variety of brain functions. For vasopressin, we demonstrated improving effects of long-term intranasal treatment on sleep in elderly people. Insulin showed improving effects of short-term memory functions. For adrenocorticotropin/melanocyte stimulating hormone, ACTH/MSH-(4-10), a twofold action was isolated: The melanocortin fragment diminished selective attention and, with subchronic administration, reduced body fat. These results could provide the basis for developing a new, specific, and "soft" neuropharmacology.
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PMID:Manipulating neuropeptidergic pathways in humans: a novel approach to neuropharmacology? 1103 13

In this study, the authors assessed the endocrine system and glucose tolerance in obese and non-obese women chronically treated with typical antipsychotic drugs (AP). In particular, we tested the hypotheses that these subjects display hypogonadism and increased insulin resistance compared to healthy weight-matched controls, as these abnormalities create a tendency towards excessive body weight gain. Twenty-six AP-treated women were matched with 26 healthy women by age, body mass index and day of the menstrual cycle. The following serum variables were evaluated in each subject: glucose tolerance after an oral glucose overload, insulin, leptin, beta-endorphin, reproductive hormones, adrenal steroids and lipids. Compared to controls, AP-treated women displayed significantly higher levels of basal glucose, insulin after 60 min of the glucose overload, prolactin, thyroid stimulating hormone and beta-endorphin, with lower levels of C-Peptide, progesterone, 17-OH progesterone, androstenedione and high-density lipoprotein cholesterol. The levels of estradiol, estrone and leptin did not differ between the groups. Thus, women treated with typical AP appeared to display more insulin resistance than healthy controls, predisposing them to excessive weight gain. Insulin sensitivity might be further impaired when the subject switches to atypical AP administration. Metformin and related agents may reduce body weight in these subjects. The high levels of the opiate beta-endorphin suggest that opiate antagonists such as naloxone and naltrexone might be useful as well. Even though the luteal phase of the menstrual cycle appears to be severely disturbed, the normal serum levels of estradiol and estrone do not support the proposal derived from animal experimental studies about the use of estrogens or tamoxifen to counteract AP-induced obesity.
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PMID:Endocrine and metabolic abnormalities involved in obesity associated with typical antipsychotic drug administration. 1177 42

Polycystic ovary syndrome (PCOS) is characterized by various endocrine and metabolic abnormalities, whose mutual associations and symptoms are still not clear. In the present study, fifteen PCOS patients and fifteen controls, matched for age and body weight, were investigated. Endocrine profiles were evaluated by the nafarelin and the adrenocorticotropin (ACTH) test. Insulin sensitivity was determined by an intravenous insulin tolerance test. Patients showed a significant predominance of abdominal adiposity [waist-to-hip ratio (WHR), 0.86 +/- 0.05 vs. 0.79 +/- 0.04] with markedly higher fasting insulin levels (+75%) and reduced insulin sensitivity (-37%). Fasting insulin, testosterone and free androgen index were positively correlated with the body mass index (BMI). In contrast, insulin sensitivity and BMI were inversely correlated in patients only. In the nafarelin test increases of 17-OH-progesterone and androstenedione were higher in patients and positively correlated with fasting insulin levels. Lipoprotein profiles showed trends towards higher triglycerides, lower HDL-cholesterol and a preponderance of small, dense LDL in patients. In PCOS higher triglycerides and lower HDL cholesterol were correlated with insulin sensitivity. It is concluded that PCOS patients show metabolic abnormalities combined with a more adroid type of adiposity when compared to cyclic controls of similar BMI.
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PMID:Body fat distribution, insulin sensitivity, ovarian dysfunction and serum lipoproteins in patients with polycystic ovary syndrome. 1191 81

Elevated plasma prolactin and mild hypocortisolemia have been observed in patients with rheumatic disorders. This study was designed to assess the potential inhibitory effect of hyperprolactinemia on hypothalamic-pituitary-adrenocortical function. Hypoglycemia was induced by intravenous insulin injection (0.1 IU/kg) in 10 female volunteers of fertile age during their follicular phase twice: 60 min after either domperidone (10 mg orally) or placebo administration. Blood samples were collected from an indwelling catheter inserted into the cubital vein at -60, 0, 30, 45, 60 and 90 min. The concentrations of prolactin, adrenocorticotropic hormone (ACTH), cortisol, epinephrine, norepinephrine and glucose were measured in plasma. Domperidone administration significantly increased plasma prolactin concentrations (71 +/- 11 ng/ml vs. 14 +/- 6 ng/ml; p <0.001), while basal plasma concentrations of ACTH, cortisol, norepinephrine and epinephrine were unaffected. Insulin-induced hypoglycemia resulted in a significant rise in the mean plasma ACTH levels from 10 +/- 1 pg/ml (domperidone) and 11 +/- 1 pg/ml (controls) to 148 +/- 19 pg/ml (domperidone) and 139 +/- 12 pg/ml (controls) at 45 min (p < 0.001), in plasma cortisol from 407 +/- 62 nmol/l (domperidone) and 391 +/- 42 nmol/l (controls) to 925 +/- 60 nmol/l (domperidone) and 810 +/- 52 nmol/l (controls) at 60 min (p < 0.001), and in plasma epinephrine from 40 +/- 26 pg/ml (domperidone) and 16 +/- 3 pg/ml (controls) to 274 +/- 55 pg/ml (domperidone) and 352 +/- 61 pg/ml (controls) at 30 min; (p < 0.001). The significant increase in ACTH, cortisol and epinephrine responses to hypoglycemia was similar in both groups. We observed mild norepinephrine response to hypoglycemia but this was irrespective of the medication. In conclusion, pharmacologically-induced hyperprolactinemia did not induce significant changes of hypothalamic-pituitary-adrenocortical function and did not influence sympathoadrenal activity in healthy young women.
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PMID:Hyperprolactinemia does not influence hypothalamic-pituitary-adrenocortical function during hypoglycemia in women. 1218 36

Combined pituitary hormone deficiency (CPHD) can be caused by mutation of the pituitary transcription factors POU1F1 or PROP1. More recently mutations in the HESX1, the LHX3 and LHX4 transcription factor genes have also been described as a cause in patients with CPHD. In most patients the disorder is characterized by an impaired production of GH, TSH, PRL and gonadotropins. In some cases of CPHD adrenocorticotropin deficiency is also present. We report the progressive CPHD and its molecular etiology in a woman with CPHD presenting with first symptoms of ACTH/cortisol deficiency at the age of 48 years. The 49 year old patient's initial symptoms were growth retardation at the age of 2 years and symptoms of hypothyroidism at the age of 5 years. The patient never entered puberty spontaneously. No familial history of delayed puberty, growth retardation or other symptoms of CPHD were present. At the age of 48 years the patient presented with the first symptoms of hypocortisolism such as recurring hypoglycaemias and hyponatriaemia with coma. Cortisol, ACTH, TSH, fT3, fT4 and GH as well as LH, FSH and PRL were measured in basal conditions. GH, cortisol and ACTH were also measured in response to an Insulin Tolerance Test. Molecular analysis was performed by PCR amplification and sequencing of exon 1-3 of the PROP1 gene. The patient had insufficiencies of TSH, LH, FSH and GH. PRL was normal. Serum cortisol was low and basal ACTH was normal. However, there were no responses of cortisol, ACTH and GH to hypoglycaemia. Magnetic resonance imaging showed a hypoplastic anterior pituitary lobe. Direct sequencing revealed a homozygous 2 base-pair deletion 301-302delAG in exon 2 of the PROP1 gene. This case suggests that in patients with CPHD ACTH producing cells may be involved at a rather late age.
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PMID:Adrenocorticotrope deficiency with clinical evidence for late onset in combined pituitary hormone deficiency caused by a homozygous 301-302delAG mutation of the PROP1 gene. 1281 7

In an attempt to probe the effect of beta-endorphin on insulin resistance, we used Wistar rats that were fed fructose-rich chow to induce insulin resistance. Insulin action on glucose disposal rate (GDR) was measured using the hyperinsulinemic euglycemic clamp technique, in which glucose (variable), insulin (40 mU/kg/min), and beta-endorphin (6 ng/kg/min) or vehicle were initiated simultaneously and continued for 120 min. A marked reduction in insulin-stimulated GDR was observed in fructose-fed rats compared to normal control rats. Infusion of beta-endorphin reversed the value of GDR, which was inhibited by naloxone and naloxonazine each at doses sufficient to block opioid mu-receptors. Opioid mu-receptors may therefore be activated by beta-endorphin to improve insulin resistance. Next, soleus muscle was isolated to investigate the effect of beta-endorphin on insulin signals. Insulin resistance in rats induced by excess fructose was associated with the impaired insulin receptor (IR), tyrosine autophosphorylation, and insulin receptor substrate (IRS)-1 protein content in addition to the significant decrease in IRS-1 tyrosine phosphorylation in soleus muscle. This impaired glucose transportation was also due to signaling defects that included an attenuated p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3-kinase) and Akt serine phosphorylation. However, IR protein levels were not markedly changed in rats with insulin resistance. beta-endorphin infusion reversed the fructose-induced decrement in the insulin-signaling cascade with increased GDR. Apart from IR protein levels, infusion of beta-endorphin reversed the decrease in protein expression for the IRS-1, p85 regulatory subunit of PI3-kinase, and Akt serine phosphorylation in soleus muscle in fructose-fed rats. The decrease in insulin-stimulated protein expression of glucose transporter subtype 4 (GLUT 4) in fructose-fed rats returned to near-normal levels after beta-endorphin infusion. Infusion of beta-endorphin may improve insulin resistance by modulating the insulin-signaling pathway to reverse insulin responsiveness.
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PMID:Infusion of beta-endorphin improves insulin resistance in fructose-fed rats. 1532 68

Allgrove syndrome is a genetic disorder inherited in an autosomal recessive pattern and characterized by a triad of adrenal insufficiency, achalasia, and alacrima. The gene affected by the mutation in patients with Allgrove syndrome is termed either AAAS or ALADIN (alacrima/achalasia/adrenal insufficiency/neurologic disorder). Adrenal insufficiency in patients with this disorder may develop as late as the third decade of life. We describe a 24-year-old female with Allgrove syndrome, in whom initial testing with 250 microg corticotropin (ACTH) stimulation test performed on 3 occasions produced normal serum cortisol values and results of the 1-microg ACTH stimulation tests performed on 6 occasions were conflicting. Insulin-induced hypoglycemia produced a nadir serum glucose value of 36 mg/dL without adequate serum cortisol stimulation, confirming presence of adrenal insufficiency. Gene sequencing identified 2 mutations in the triple A gene: an IVSC14 + 1 G to A mutation, which has been previously reported, and a novel R155P exon 6 mutation. We conclude that a novel R155P mutation in the ALADIN gene is associated with Allgrove syndrome and that insulin-induced hypoglycemia, rather than ACTH stimulation tests, should be used for accurate diagnosis of adrenal insufficiency in this disorder.
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PMID:The diagnosis of adrenal insufficiency in a patient with Allgrove syndrome and a novel mutation in the ALADIN gene. 1569 Mar 14

beta-Endorphin and a C-terminal analogue have been shown to decrease muscle fatigue and increase glucose uptake in muscles of normal mice. In order to provide evidence whether these peptides might be useful in muscle-wasting conditions and whether the two actions of the peptides are interdependent, the effect of beta-endorphin on muscle fatigue and glucose uptake was studied using isolated hemidiaphragm preparations of dystrophic mice as well as normal mice. Muscle contractions were elicited by high-frequency stimulation of the phrenic nerve. Glucose uptake was measured using (nonmetabolizable) 2-deoxy-D-[1-(3)H]glucose. beta-Endorphin and the C-terminal analogue reduced fatigue in normal muscles of males but not females. Insulin had no effect in either sex. The peptides increased 2-deoxyglucose uptake in contracting and noncontracting muscles of normal males and females. beta-Endorphin reduced fatigue and increased deoxyglucose uptake in dystrophic muscles. The effect on fatigue was not due to increased glucose uptake, as the energy substrate present was pyruvate. Nerve stimulation released beta-endorphin immunoreactivity from intramuscular nerves of dystrophic mice. It is hypothesized that beta-endorphin released from motor nerves as well as from the pituitary could be responsible for improving muscle function during exercise. beta-Endorphin or analogues could have therapeutic use in muscle-wasting disease.
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PMID:Beta-endorphin decreases fatigue and increases glucose uptake independently in normal and dystrophic mice. 1570 44


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