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)

Obese mice (C57BL/6J ob/ob) and their lean littermates were studied at various ages from immediately post weaning until 62 weeks of age, at which mortality increased markedly. Several age-related changes were noted. 1) Plasma glucose levels were elevated in obese mice 5-20 weeks and 62 weeks of age, but were similar to those in the lean mice at 20-60 weeks of age. Plasma insulin levels were elevated in obese mice, and there were no age-related differences. 2) Brain serotonin was elevated in obese mice at all ages and increased with age in both obese and lean animals. 3) Pituitary contents of ACTH and beta-endorphin were elevated in young obese mice and increased further as these mice approached their life expectancy. 4) The ratios of ACTH to beta-endorphin immunoreactivities were similar in obese and lean mice, except in obese mice over 50 weeks of age where this ratio was increased. We conclude that: 1) the obese mouse is characterized by hyperinsulinemia and hyperadrenocorticism throughout its life; 2) the insulin resistance of the obese mouse improves at 20 weeks of age, yet deteriorates as its life expectancy is approached; 3) the obese mouse has an elevated brain serotonin content similar to previously described elevations of the putative neurotransmitters dopamine and norepinephrine in these mice; and 4) as the obese mouse approaches its life expectancy, abnormalities may occur in the synthesis, processing, or secretion of ACTH and/or beta-endorphine.
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PMID:A longitudinal hormonal profile of the genetically obese mouse. 624 69

Genetically obese mice (C57BL/6J-ob/ob), fed ad libitum, demonstrated a precipitous increase in the spontaneous death rate after 50 weeks. The first signs of morbidity were a ruffled hair coat and a progressive motor ataxia. Necropsy revealed that obese mice had pale and fatty livers, urolithiasis and grossly distended bladders. Microscopically, the hepatocellular changes observed in all aged obese mice included: a loss of orientation of hepatocytes, an enormous variability in the size of both hepatocytes and their nuclei, and an extensive deposition of both large and small lipid droplets, confirmed by an increase content of triacylglycerols. A subacute-to-chronic, multifocal, necrotizing hepatitis was also present. Kidneys from aged obese mice contained hypertrophied glomeruli and increased PAS-stained material. Tubular dilation with compaction of the tubular cells was also seen. There were no significant alterations in the microanatomy or mineralization of femurs from obese mice, yet there was a significant increase in plasma alkaline phosphatase activity. In obese mice at 62-63 weeks of age, hyperglycemia was present even in spite of hyperinsulinemia. Pituitary immunoreactive ACTH and its molar ratio to pituitary immunoreactive beta-endorphin were also increased in obese mice at this age. Even though the etiology of the decreased lifespan of genetically obese mice remains uncertain, the possibility is discussed that an overall defect in the central nervous system may be involved.
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PMID:Hormonal, metabolic and morphologic studies of aged C57BL/6J obese mice. 673 67

Neuropeptide Y (NPY), a major brain neurotransmitter, is expressed in neurons of the hypothalamic arcuate nucleus (ARC) that project mainly to the paraventricular nucleus (PVN), an important site of NPY release. NPY synthesis in the ARC is thought to be regulated by several factors, notably insulin, which may exert an inhibitory action. The effects of NPY injected into the PVN and other sites include hyperphagia, reduced energy expenditure and enhanced weight gain, insulin secretion, and stimulation of corticotropin and corticosterone release. The ARC-PVN projection appears to be overactive in insulin-deficient diabetic rats, and could contribute to the compensatory hyperphagia and reduced energy expenditure, and pituitary dysfunction found in these animals; overactivity of these NPY neurons may be due to reduction of insulin's normal inhibitory effect. The ARC-PVN projection is also stimulated in rat models of obesity +/- non-insulin diabetes, possibly because the hypothalamus is resistant to inhibition by insulin; in these animals, enhanced activity of ARC NPY neurons could cause hyperphagia, reduced energy expenditure, and obesity, and perhaps contribute to hyperinsulinemia and altered pituitary secretion. Overall, these findings suggest that NPY released in the hypothalamuss, especially from the ARC-PVN projection, plays a key role in the hypothalamic regulation of energy balance and metabolism. NPY is also found in the human hypothalamus. Its roles (if any) in human homeostasis and glucoregulation remain enigmatic, but the animal studies have identified it as a potential target for new drugs to treat obesity and perhaps NIDDM.
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PMID:Neuropeptide Y, the hypothalamus, and diabetes: insights into the central control of metabolism. 747 13

Several dominant mutations at the murine agouti locus result in the expression of a number of phenotypic changes, including a predominantly yellow coat color, obesity, and hyperinsulinemia. The mutants exhibit ectopic overexpression of normal agouti protein, suggesting that agouti regulates coat coloration by direct antagonism of the alpha-melanocyte-stimulating hormone receptor. We have tested this hypothesis by examining agouti inhibition of both melanocortin-stimulated cyclic adenosine monophosphate production and the binding of a radioactive melanocortin analog in the murine B16F10 melanoma cell line. Inhibition of melanocortin-induced cyclic nucleotide accumulation did not require preincubation of the cells with agouti and was independent of the agonist used. Furthermore, inhibition of both agonist binding to and activation of melanocortin receptor could be described by a simple competitive model with similar inhibition constants of 1.9 and 0.9 nM, respectively. The mutually exclusive binding of agouti and melanocortin was verified by cross-linking experiments using a radiolabeled alpha-melanocyte-stimulating hormone analog. Competitive inhibition of alpha-melanocyte-stimulating hormone binding can account for the effects of agouti on coat coloration and suggests the possibility that the other phenotypic changes observed on agouti overexpression may be due to direct action of agouti at a novel melanocortin receptor(s).
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PMID:Agouti antagonism of melanocortin binding and action in the B16F10 murine melanoma cell line. 754 13

The concentrations of beta-endorphin, ACTH, insulin (IRI), glucagon (IRG), cortisol and growth hormone were determined by radioimmunoassay during oral glucose tolerance test (OGTT) performed in 13 obese patients with normal glucose tolerance and without arterial hypertension. The test was performed in random, before and after intravenous administration of 0.8 mg of naloxone. Six persons with normal body weight served as controls. Higher basal concentrations of beta-endorphin and significant increase in beta-endorphin levels during OGTT, without concomitant increase in ACTH concentrations, have been found in obese patients. No effect of naloxone on beta-endorphin liberation during OGTT was observed, though the drug caused lowering in maximal increment of beta-endorphin and paradoxically lowered the concentrations of ACTH and cortisol. The basal concentrations of beta-endorphin did not correlate with the concentrations of insulin, ACTH, cortisol and growth hormone. Elevated concentrations of insulin, lowered concentration of growth hormone and normal levels of glucose and glucagon were observed in basal conditions, and excessive responses of insulin, glucose and glucagon were observed in obese patients during OGTT. Naloxone lowered insulin response and inhibited the fall of growth hormone during OGTT but did not influence the concentrations of glucose and glucagon. No correlation was found during OGTT after naloxone between insulin and beta-endorphin, ACTH or cortisol, whereas negative correlation was observed between insulin and growth hormone. The obtained results suggest that the elevated concentrations of beta-endorphin in simple obesity may be of both hypophyseal and peripheral origin. Hyper-beta-endorphinemia observed in obesity is probably not directly responsible for hyperinsulinemia, it may, however, be responsible for lower sensitivity of tissues to the action of insulin.
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PMID:[Effect of naloxone on beta-endorphin and insulin concentrations during glucose tolerance testing in patients with simple obesity]. 805 20

Female adolescence is normally accompanied by increased adrenal and ovarian production of androgens. Indeed it is not uncommon in early to midpuberty to see typical features of adult polycystic ovary syndrome, with luteinizing hormone-driven ovarian hyperandrogenism, hyperinsulinemia, acne, anovulation, oligomenorrhea, and large, multifollicular ovaries. Unfortunately, no single prospective test can differentiate girls in whom this maturational stage is self-limited from those in whom it will progress to adult polycystic ovary syndrome with hirsutism and anovular infertility. An occasional hirsute adolescent will prove by corticotropin testing to have a nonclassical variant of adrenal 21-hydroxylase deficiency and will benefit from glucocorticoid therapy. The prevalence or even the existence of mild 11 beta-hydroxylase or 3 beta-hydroxysteroid dehydrogenase deficiency is more problematic. Given these difficulties of exact diagnosis and prognosis, therapy for the adolescent with mild hirsutism, acne, or oligomenorrhea should be conservative.
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PMID:Hyperandrogenism in female adolescents. 837 78

Evidence for an intrinsic effect of insulin on the central nervous system is accumulating. To test the hypothesis that insulin per se may modulate neuroendocrine counterregulation, hypoglycemia perception, and cerebral function in insulin-dependent diabetes mellitus, we examined 27 patients without any sign of classical autonomic neuropathy or evidence of so-called hypoglycemia unawareness. We used the hyperinsulinemic (0.67 vs. 2.00 mU/kg.min), stepped hypoglycemic (5.6/3.5/2.4/2.0 mmol/L) clamp technique to assess the patient's awareness of and response to equivalent hypoglycemic stimuli under different degrees of physiological hyperinsulinemia (approximately 270 vs. approximately 810 pmol/L) after an overnight euglycemic clamp (5.6 mmol/L). Simultaneously, the patient's cerebral function was assessed from his electrophysiological activity and neuropsychological skills. Higher degrees of physiological hyperinsulinemia caused enhanced neuroendocrine response (adrenaline, P < 0.05; noradrenaline, P < 0.03; GH, P < 0.02; beta-endorphin, P < 0.03; ACTH, P = 0.12; cortisol, P = 0.06; PRL, P = 0.08) and symptom awareness (total symptoms, P < 0.04; autonomic symptoms, P < 0.02; neuroglycopenia symptoms, P < 0.05; sweating, P < 0.05; heart pounding, P < 0.02; trembling, P < 0.01; lack of concentration, P < 0.02) to occur. Deteriorations of electrophysiological activity (middle latency auditory-evoked potentials, P < 0.04; Pa peak latencies, P < 0.05; Pa-V interpeak latencies, P = 0.08) and neuropsychological skills (Stroop test, P < 0.05; trail making, P = 0.12) were more pronounced the higher the insulin level, but at similar blood glucose concentrations. We conclude that insulin-associated modulation of neuroendocrine counterregulation, hypoglycemia perception, and cerebral function may occur in insulin-dependent diabetes mellitus, which indicates an intrinsic effect of insulin on the human brain.
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PMID:Insulin-associated modulation of neuroendocrine counterregulation, hypoglycemia perception, and cerebral function in insulin-dependent diabetes mellitus: evidence for an intrinsic effect of insulin on the central nervous system. 877

To investigate the relationship between elevated LH, hyperinsulinemia and neuropeptides in polycystic ovarian syndrome (PCOS), we measured the endogenous levels of insulin, somatostatin (SS), beta-endorphin (beta-EP) and dynorphin A (Dyn A) before and after a glucose load in three groups: group 1 (LH/ FSH > or = 3, n = 30); group 2 (LH/FSH < 3, n = 25), and controls (n = 15). In the basal state, significantly negative correlations were found between LH and SS (r = -0.51, p < 0.05) in group 1 and between LH and beta-EP (r = -0.49, p < 0.05) in group 2. After a glucose load, PCOS women had greater beta-EP and Dyn A responses in group 1 and impaired SS response in group 2 as compared with the control. The data suggest endogenously lower SS, higher beta-EP and Dyn A may contribute to the elevation of LH and insulin secretions in PCOS.
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PMID:Responses of somatostatin, beta-endorphin and dynorphin A to a glucose load in two groups of women with polycystic ovarian syndrome. 887 Nov 83

The adrenal response to adrenocorticotropic hormone (ACTH) stimulation and dexamethasone (DEX) inhibition tests in six healthy ovulatory control women (31.6 +/- SD 0.6 years old) with a body mass index (BMI) of 24.8 +/- 1.3 kg/m2 (Group 1) were compared against seven women (28.1 +/- 0.8 years old, BMI 30.9 +/- 2.1 kg/m2) with polycystic ovary syndrome (PCOS) and hyperinsulinism (Group 2). In both groups the following tests were performed: a) a 100-g 2-h oral glucose tolerance test (OGTT) with serum glucose and insulin measurements; b) an ACTH stimulation test (2-h 0.25 mg iv bolus); and c) a 1 mg oral midnight DEX inhibition test. Assays of serum cortisol. 17-hydroxyprogesterone, dehydroepiandrosterone sulfate (DHEA-S), free testosterone (FT), and androstenedione during the ACTH and DEX tests were performed. Contrary to Group 1, Group 2 showed: a) higher basal luteinizing hormone follicle-stimulating hormone ratio, FT, and insulin, and hyperinsulinism during the OGTT; b) FT significantly higher after ACTH; and c) FT and DHEAS did not show a significant inhibition with DEX. Our results suggest a certain degree of adrenal participation in the pathogenesis of the hyperandrogenism in these women, which may be the final expression of a synergistic stimulation of the adrenals by hyperinsulinism, relatively high LH, and chronic hyperestrogenism, all of which are present virtually in all women with PCOS.
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PMID:[Androgen response in women with polycystic ovary syndrome and hyperinsulinemia during stimulation with corticotrophin and inhibition with dexamethasone]. 896 89

The growth hormone (GH) response to stimulation tests is impaired in obesity. Moreover, obese patients exhibit a "paradoxical" increase of GH to GH-releasing hormone (GHRH) stimulation after food ingestion; this paradoxical response is reversed by naloxone infusion. On the other hand, beta-endorphin seems to exert profound effects on insulin release. Recent studies also demonstrated an impairment of GH response to several stimuli in polycystic ovary syndrome (PCOS), a condition associated with obesity, hyperinsulinism, and insulin resistance. Chronic inhibition of opioid tone by the opioid antagonist naltrexone (NTX) is able to reduce the insulin response to an oral glucose tolerance test (OGTT) in hyperinsulinemic PCOS patients. Since insulin and GH may reciprocally influence their secretion and the opioid system may have a role in the pathogenesis of hyperinsulinemia and reduced GH secretion, we have explored the involvement of these neuroendocrine mechanisms in essential obesity and in obesity associated with hyperandrogenism by a long-term treatment with an opiate antagonist. We tested seven obese patients affected by PCOS, seven matched women with essential obesity (EO), and five non-obese control subjects. All patients, in the follicular phase, underwent an OGTT (75 g) and basal hormone assay. Two days later, patients were subjected to a GHRH test. The patients then had 4 weeks of treatment with NTX 50 mg/d. Following continuation of the treatment, OGTT and GHRH tests were repeated. Insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) plasma concentrations were also determined in the basal condition before and after NTX treatment. NTX treatment reduced fasting insulin levels in patients with EO (P < .05) and restored a normal GH response to GHRH without affecting IGF-1 and IGFBP-3 levels. In PCOS subjects, NTX reduced the insulin response to a glucose load and failed to modify the blunted GH response to GHRH. Our data suggest a significant difference in opioid system function in PCOS and EO subjects, indicating a particular form of obesity in PCOS. The opiate antagonist treatment in EO may act through the reduction of negative insulin feedback on GH secretion. In PCOS patients, the failure to improve GH secretion in obese hyperandrogenized patients may be related to a high opioidergic tone or to the inhibitory predominance of other neurotransmitters.
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PMID:Impact of long-term naltrexone treatment on growth hormone and insulin secretion in hyperandrogenic and normal obese patients. 916 Aug 21


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