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Find video protocols related to scientific articles indexed in Pubmed.
Ten weeks of aerobic training does not result in persistent changes in VLDL triglyceride turnover or oxidation in healthy men.
Eur. J. Endocrinol.
PUBLISHED: 08-12-2014
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Very low density lipoprotein triglyceride (VLDL-TG) and free fatty acids (FFA) constitute a substantial proportion of human energy supply both at rest and during exercise. Exercise acutely decreases VLDL-TG concentration, and VLDL-TG clearance is increased after an exercise bout. However, the effects of long-term training are not clear.
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Kinetics and utilization of lipid sources during acute exercise and acipimox.
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 06-03-2014
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Overweight is associated with abnormalities of lipid metabolism, many of which are reversed by exercise. We investigated the impact of experimental antilipolysis and acute exercise on lipid kinetics and oxidation from VLDL-TG, plasma FFA, and "residual lipids" in overweight men (n = 8) using VLDL-TG and palmitate tracers in combination with muscle biopsies in a randomized, placebo-controlled design. Participants received placebo or acipimox on each study day (4 h of rest, 90 min of exercise at 50% V(O(2 max))). Exercise suppressed VLDL-TG secretion significantly during placebo but not acipimox (placebo-rest: 64.2 ± 9.4; placebo-exercise: 48.3 ± 8.0; acipimox-rest: 55.2 ± 13.4; acipimox-exercise: 52.0 ± 10.9). Resting oxidation of VLDL-TG FA and FFA was significantly reduced during acipimox compared with placebo, whereas "residual lipid oxidation" increased significantly [VLDL-TG oxidation (placebo: 18 ± 3 kcal/h; acipimox: 11 ± 2 kcal/h), FFA oxidation (placebo: 14 ± 2 kcal/h; acipimox: 4 ± 0.5 kcal/h), and residual lipid oxidation (placebo: 3 ± 5 kcal/h; acipimox: 14 ± 5 kcal/h)]. Additionally, during exercise on both placebo and acipimox, oxidation of VLDL-TG and FFA increased, but the relative contribution to total lipid oxidation diminished, except for FFA, which remained unchanged during acipimox. Residual lipid oxidation increased significantly during exercise in both absolute and relative terms. Changes in selected cellular enzymes and proteins provided no explanations for kinetic changes. In conclusion, suppressed FFA availability blunts the effect of exercise on VLDL-TG secretion and modifies the contribution of lipid sources for oxidation.
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Validity of the International Classification of Diseases, 10th revision discharge diagnosis codes for hyponatraemia in the Danish National Registry of Patients.
BMJ Open
PUBLISHED: 04-25-2014
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To examine the validity of the International Classification of Diseases, 10th revision (ICD-10) codes for hyponatraemia in the nationwide population-based Danish National Registry of Patients (DNRP) among inpatients of all ages.
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[Acromegaly masked by symptomatic hyperprolactinaemia.]
Ugeskr. Laeg.
PUBLISHED: 03-18-2014
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A 48-year-old woman presented with galactorrhoea, moderate hyperprolactinaemia (0.97 IU/l) and a pituitary macroadenoma (10 × 7 × 6 mm). Over a period of six years the patient had developed overt acromegalic features and was subsequently diagnosed with acromegaly while treated with dopamine receptor agonist. Acromegaly should always be considered in patients presenting with hyperprolactinaemia and a pituitary adenoma.
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[Dopamin agonist treatment and fibrotic heart valve disease in hyperprolactinaemia patients.]
Ugeskr. Laeg.
PUBLISHED: 03-18-2014
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Treatment with dopamin agonists, particularly cabergoline, is the primary and preferred therapy for prolactinomas and symptomatic hyperprolactinaemia due to its effectiveness and tolerability. However, an association has been demonstrated between fibrotic heart valve disease and high-dose dopamin agonist use in patients with Parkinson's disease in several echocardiographic studies. Such observations have prompted a number of studies of valvular function in cabergoline-treated hyperprolactinaemia patients. These studies have failed to show an increased prevalence of clinically significant valvular regurgitation.
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[Genetic screening for mutations enables early diagnosis of pituitary adenomas.]
Ugeskr. Laeg.
PUBLISHED: 03-18-2014
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Mutations in the aryl hydrocarbon receptor interaction protein gene (AIP) occur in familial pituitary adenomas as an autosomal dominant inheritance with a 15-30% penetrance. The AIP mutation-associated pituitary adenomas are generally large, the onset of disease is early and treatment failure frequent. Genetic screening is also offered in Denmark and enables the detection of mutation carriers, and thus early diagnosis and treatment. Mutations have been recorded among Danish patients and their families.
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Dissecting adipose tissue lipolysis: molecular regulation and implications for metabolic disease.
J. Mol. Endocrinol.
PUBLISHED: 02-27-2014
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Lipolysis is the process by which triglycerides (TGs) are hydrolyzed to free fatty acids (FFAs) and glycerol. In adipocytes, this is achieved by sequential action of adipose TG lipase (ATGL), hormone-sensitive lipase (HSL), and monoglyceride lipase. The activity in the lipolytic pathway is tightly regulated by hormonal and nutritional factors. Under conditions of negative energy balance such as fasting and exercise, stimulation of lipolysis results in a profound increase in FFA release from adipose tissue (AT). This response is crucial in order to provide the organism with a sufficient supply of substrate for oxidative metabolism. However, failure to efficiently suppress lipolysis when FFA demands are low can have serious metabolic consequences and is believed to be a key mechanism in the development of type 2 diabetes in obesity. As the discovery of ATGL in 2004, substantial progress has been made in the delineation of the remarkable complexity of the regulatory network controlling adipocyte lipolysis. Notably, regulatory mechanisms have been identified on multiple levels of the lipolytic pathway, including gene transcription and translation, post-translational modifications, intracellular localization, protein-protein interactions, and protein stability/degradation. Here, we provide an overview of the recent advances in the field of AT lipolysis with particular focus on the molecular regulation of the two main lipases, ATGL and HSL, and the intracellular and extracellular signals affecting their activity.
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Prolonged erythropoietin treatment does not impact gene expression in human skeletal muscle.
Muscle Nerve
PUBLISHED: 01-21-2014
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Introduction: We assessed the presence of erythropoietin receptor (Epo-R) in human skeletal muscle and alterations in gene expression after prolonged erythropoiesis-stimulating agent (ESA). Methods: Nine healthy men were treated with ESA for 10 weeks (Darbepoietin-?). Muscle biopsies were collected before and after treatment. Alterations in gene expression were evaluated by gene array. Western blotting and PCR analysis evaluated Epo-R presence in human skeletal muscle. Results: Very low Epo-R mRNA levels were found, but a new and sensitive antibody did not identify Epo-R protein in human skeletal muscle. The between-subject variation in skeletal muscle gene expression was larger than the changes observed in response to prolonged ESA treatment. Conclusion: Erythropoietin is unlikely to exert direct effects in human skeletal muscle due to a lack of Epo-R protein. Furthermore, prolonged ESA treatment does not seem to exert either direct or indirect effects on skeletal muscle gene expression. © 2014 Wiley Periodicals, Inc.
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Acromegaly according to the Danish National Registry of Patients: how valid are ICD diagnoses and how do patterns of registration affect the accuracy of registry data?
Clin Epidemiol
PUBLISHED: 01-01-2014
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The incidence of acromegaly is uncertain, since population-based studies are few. In the absence of a specific acromegaly registry, the Danish National Registry of Patients (DNRP) becomes a potential source of data for studying the epidemiology of acromegaly, by linking all hospital discharge diagnoses to the personal identification numbers of individual Danish inhabitants. The validity of the DNRP with respect to acromegaly, however, remains to be tested. The aim of this study was to validate the International Classification of Diseases (ICD) codes for acromegaly (ICD-8: 25300, 25301. ICD-10: E22.0) as used in the DNRP, and to assess the influence of various registration patterns on the accuracy of registry data.
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Fasting increases human skeletal muscle net phenylalanine release and this is associated with decreased mTOR signaling.
PLoS ONE
PUBLISHED: 01-01-2014
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Fasting is characterised by profound changes in energy metabolism including progressive loss of body proteins. The underlying mechanisms are however unknown and we therefore determined the effects of a 72-hour-fast on human skeletal muscle protein metabolism and activation of mammalian target of rapamycin (mTOR), a key regulator of cell growth.
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Serum levels of bioactive IGF1 and physiological markers of ageing in healthy adults.
Eur. J. Endocrinol.
PUBLISHED: 11-02-2013
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Senescent changes in body composition and muscle strength are accompanied by reduced production of GH and IGF1, but the causal relationship remains elusive. We speculate that serum bioactive IGF1, measured by the IGF1 kinase receptor activation assay, is closer related to human physiological ageing than total IGF1 measured by immunoassay.
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Inflammatory adipokines contribute to insulin resistance in active acromegaly and respond differently to different treatment modalities.
Eur. J. Endocrinol.
PUBLISHED: 10-05-2013
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Active acromegaly is associated with insulin resistance, but it is uncertain whether inflammation in adipose tissue is a contributing factor.
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Growth hormone-induced insulin resistance in human subjects involves reduced pyruvate dehydrogenase activity.
Acta Physiol (Oxf)
PUBLISHED: 08-13-2013
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Insulin resistance induced by growth hormone (GH) is linked to promotion of lipolysis by unknown mechanisms. We hypothesized that suppression of the activity of pyruvate dehydrogenase in the active form (PDHa) underlies GH-induced insulin resistance similar to what is observed during fasting.
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Whole body metabolic effects of prolonged endurance training in combination with erythropoietin treatment in humans: a randomized placebo controlled trial.
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 08-06-2013
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Erythropoietin (Epo) administration improves aerobic exercise capacity and insulin sensitivity in renal patients and also increases resting energy expenditure (REE). Similar effects are observed in response to endurance training. The aim was to compare the effects of endurance training with erythropoiesis-stimulating agent (ESA) treatment in healthy humans. Thirty-six healthy untrained men were randomized to 10 wk of either: 1) placebo (n = 9), 2) ESA (n = 9), 3) endurance training (n = 10), or 4) ESA and endurance training (n = 8). In a single-blinded design, ESA/placebo was injected one time weekly. Training consisted of biking for 1 h at 65% of wattmax three times per week. Measurements performed before and after the intervention were as follows: body composition, maximal oxygen uptake, insulin sensitivity, REE, and palmitate turnover. Uncoupling protein 2 (UCP2) mRNA levels were assessed in skeletal muscle. Fat mass decreased after training (P = 0.003), whereas ESA induced a small but significant increase in intrahepatic fat (P = 0.025). Serum free fatty acid (FFA) levels and palmitate turnover decreased significantly in response to training, whereas the opposite pattern was found after ESA. REE corrected for lean body mass increased in response to ESA and training, and muscle UCP2 mRNA levels increased after ESA (P = 0.035). Insulin sensitivity increased only after training (P = 0.011). In conclusion: 1) insulin sensitivity is not improved after ESA treatment despite improved exercise capacity, 2) the calorigenic effects of ESA may be related to increased UCP2 gene expression in skeletal muscle, and 3) training and ESA exert opposite effects on lipolysis under basal conditions, increased FFA levels and liver fat fraction was observed after ESA treatment.
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Resveratrol in metabolic health: an overview of the current evidence and perspectives.
Ann. N. Y. Acad. Sci.
PUBLISHED: 07-17-2013
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In the search for novel preventive and therapeutic modalities in the management of metabolic diseases and obesity, resveratrol has attracted great attention over the past decades. Preclinical trials suggest that resveratrol mimics the metabolic effects of calorie restriction (CR) via activation of silent mating type information regulation 2 homolog 1 (SIRT1). In experimental animals, this potential translates into prevention or improvement of glucose metabolism, anti-inflammation, cancer, and nonalcoholic fatty liver disease. Moreover, and in accordance with CR, supplementation with resveratrol promotes longevity in several primitive species and protects against diet-induced metabolic abnormalities in rodents. Despite the substantial preclinical evidence, human clinical data are very scarce, and even though the compound is widely distributed as an over-the-counter human nutritional supplement, its therapeutic rationale has not been well characterized. In this review, we provide a brief overview of the field and discuss the future scientific directions of resveratrol research.
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Gene expression in skeletal muscle after an acute intravenous GH bolus in human subjects: identification of a mechanism regulating ANGPTL4.
J. Lipid Res.
PUBLISHED: 04-20-2013
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Growth hormone (GH) acutely stimulates lipolysis and fat oxidation, a process that operates postabsorptively and involves activation of the JAK-STAT pathway in the target tissue; no in vivo data exist regarding subsequent GH-regulated gene transcription. We obtained serum samples and muscle biopsies in human subjects before and 2 h after administration of a GH bolus. A significant (~75%) elevation in serum FFA levels was recorded post GH. Microarray identified 79 GH-regulated genes in muscle. With qRT-PCR, we then examined the expression of selected genes in the presence and absence of glucose-induced suppression of lipolysis. Four genes involved in the JAK-STAT5 signaling pathway were regulated by GH, including SOCS1-3 and CISH, in addition to three genes associated with insulin action: NF?B1A, PIK3C2B, and PRKAG2. The gene encoding ANGPTL4, a protein involved in lipolysis and suppression of LPL activity, exhibited the most pronounced upregulation (5.6-fold) after GH, which was abrogated by concomitant suppression of lipolysis. Therefore, the GH-induced stimulation of ANGPTL4 gene expression seems secondary to induction of lipolysis. This new concept implies that abundant supply of circulating FFA decreases the need for alternative triglyceride-derived FFA through distinct inhibition of LPL mediated by increased ANGPTL4 gene expression in human muscle.
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Simultaneous determination of ?-hydroxybutyrate and ?-hydroxy-?-methylbutyrate in human whole blood using hydrophilic interaction liquid chromatography electrospray tandem mass spectrometry.
Clin. Biochem.
PUBLISHED: 04-16-2013
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For the quantification of ?-hydroxybutyrate (BHB) and ?-hydroxy-?-methylbutyrate (HMB) in human whole blood, a method using hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC-MS/MS) was developed, which does not require chemical modification of the analytes.
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Acute peripheral tissue effects of ghrelin on interstitial levels of glucose, glycerol, and lactate: a microdialysis study in healthy human subjects.
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 04-16-2013
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Ghrelin is a gut-derived peptide and an endogenous ligand for the ghrelin receptor. Intravenous infusion of ghrelin induces insulin resistance and hyperglycemia and increases circulating levels of nonesterified free fatty acids. Our objective was to investigate whether the metabolic effects are mediated directly by ghrelin in skeletal muscle and adipose (peripheral and central) tissues. Ten healthy men (24.9 ± 1.3 yr) received 300 min of supraphysiological ghrelin administration by microdialysis catheters in skeletal muscle and adipose tissues in a randomized, single-blind, and placebo-controlled study. Microdialysis perfusates were analyzed every 30 min for glucose, glycerol, and lactate during both a basal period and a hyperinsulinemic euglycemic clamp. The primary outcome measures were interstitial concentrations of glucose, glycerol, and lactate in skeletal muscle and adipose tissues. Interstitial concentrations of glucose were similar in skeletal muscle, peripheral, and central adipose tissue in the basal period. During hyperinsulinemia, interstitial concentrations of glucose in skeletal muscle decreased in response to ghrelin exposure [2.84 ± 0.25 (ghrelin) vs. 3.06 ± 0.26 mmol/l (placebo), P = 0.04]. Ghrelin exposure did not impact on interstitial concentrations of glycerol and lactate. We conclude that ghrelin administration into skeletal muscle decreases interstitial concentrations of glucose during euglycemic hyperinsulinemia, which is indicative of increased insulin sensitivity without any effects on interstitial glycerol levels in either muscle or adipose tissue. These data contrast with the metabolic effects of ghrelin observed after systemic exposure and suggest the existence of a second messenger that remains to be identified.
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Use of glucocorticoids and risk of venous thromboembolism: a nationwide population-based case-control study.
JAMA Intern Med
PUBLISHED: 04-03-2013
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Excess endogenous cortisol has been linked to venous thromboembolism (VTE) risk, but whether this relationship applies to exogenous glucocorticoids remains uncertain. Because the prevalence of glucocorticoid use and the incidence of VTE are high, an increased risk of VTE associated with glucocorticoid use would have important implications.
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Multisystem morbidity and mortality in Cushings syndrome: a cohort study.
J. Clin. Endocrinol. Metab.
PUBLISHED: 03-26-2013
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Cushings syndrome (CS) is associated with hypercoagulability, insulin resistance, hypertension, bone loss, and immunosuppression. To date, no adequately large cohort study has been performed to assess the multisystem effects of CS.
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Circulating levels of pegvisomant and endogenous growth hormone during prolonged pegvisomant therapy in patients with acromegaly.
Clin. Endocrinol. (Oxf)
PUBLISHED: 02-18-2013
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To investigate whether pegvisomant treatment in acromegaly induces gradual elevations in endogenous serum growth hormone (GH) levels and whether serum pegvisomant levels predict the therapeutic outcome.
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Acute peripheral metabolic effects of intraarterial leg infusion of somatostatin in healthy young men.
J. Clin. Endocrinol. Metab.
PUBLISHED: 06-01-2011
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Evidence suggests that somatostatin not only inhibits the secretion of GH but also suppresses GH action in peripheral tissues.
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Long-term DHEA substitution in female adrenocortical failure, body composition, muscle function, and bone metabolism: a randomized trial.
Eur. J. Endocrinol.
PUBLISHED: 05-23-2011
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Adrenal derived androgens are low in women with adrenal failure. The physiological consequences of substitution therapy are uncertain.
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Novel serum protein biomarkers indicative of growth hormone doping in healthy human subjects.
Proteomics
PUBLISHED: 02-09-2011
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The detection of recombinant human growth hormone (rhGH) is difficult due to its short half-life; therefore, novel and robust biomarkers of rhGH abuse are needed. In this study, serum samples derived from subjects treated with rhGH in a randomized, double blind, placebo-controlled crossover study were analyzed by 2-DE coupled with MS. Eight healthy male subjects aged 23.2±0.6 years were injected with rhGH (2?mg/day) or saline for 7 days with serum samples drawn at days 0, 3, and 8. Protein intensities were quantified and analyzed for differences between rhGH and placebo treatments. Proteins that showed significant changes were identified and confirmed by Western blotting. These included specific isoforms of ?-1 antitrypsin and transthyretin that increased; and inter-?-trypsin inhibitor heavy chain H4, apolipoprotein A-1, and hemoglobin ? chain that decreased. These proteins represent novel biomarkers of short-term rhGH exposure and may lead to a new method for detecting rhGH doping.
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Novel serum biomarkers for erythropoietin use in humans: a proteomic approach.
J. Appl. Physiol.
PUBLISHED: 10-21-2010
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Erythropoietin (Epo) is produced primarily in the kidneys upon low blood oxygen availability and stimulates erythropoiesis in the bone marrow. Recombinant human Epo (rHuEpo), a drug developed to increase arterial oxygen content in patients, is also illicitly used by athletes to improve their endurance performance. Therefore, a robust and sensitive test to detect its abuse is needed. The aim of the present study was to investigate potential human serum biomarkers of Epo abuse employing a proteomic approach. Eight healthy male subjects were injected subcutaneously with rHuEpo (5,000 IU) every second day for a 16-day period. Serum was collected before starting the treatment regime and again at days 8 and 16 during the treatment period. Samples were homogenized and proteins separated by two-dimensional gel electrophoresis (2DE). Spots that changed significantly in response to rHuEpo treatment were identified by mass spectrometry. Both the number of reticulocytes and erythrocytes increased throughout the study, leading to a significant increase in hematocrit and hemoglobin content. In addition, transferrin levels increased but the percentage of iron bound to transferrin and ferritin levels decreased. Out of 97 serum proteins, seven were found to decrease significantly at day 16 compared with pre-Epo administration, and were identified as four isoforms of haptoglobin, two isoforms of transferrin, and a mixture of hemopexin and albumin. In support, total serum haptoglobin levels were found to be significantly decreased at both days 8 and 16. Thus a 2DE proteomic approach for discovery of novel markers of Epo action appears feasible.
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Epidemiology of Cushings syndrome.
Neuroendocrinology
PUBLISHED: 09-10-2010
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Overt Cushings syndrome is a rare disorder with an annual incidence of 2-3/million of which benign adrenal adenomas account for 0.6/million. The female:male ratio is 3:1. Preliminary data indicate a high proportion of subclinical Cushings syndrome in certain risk populations such as patients with type 2 diabetes or osteoporosis. The clinical implications of these observations are presently unclear. Surgery remains first line treatment for overt disease and initial cure or remission is obtained in 65-85% of patients with Cushings disease. Late recurrences, however, occur in up to 20% and the risk does not seem to plateau even after 20 years of follow-up. A 2- to 3-fold increase in mortality is observed in most studies, and this excess mortality seems confined to patients in whom initial cure was not obtained. Cushings syndrome continues to pose diagnostic and therapeutic challenges and life-long follow-up is mandatory.
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Conventional and novel biomarkers of treatment outcome in patients with acromegaly: discordant results after somatostatin analog treatment compared with surgery.
Eur. J. Endocrinol.
PUBLISHED: 09-02-2010
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Control of disease activity in acromegaly is critical, but the biochemical definitions remain controversial.
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Decreased lipid intermediate levels and lipid oxidation rates despite normal lipolysis in patients with hypothyroidism.
Thyroid
PUBLISHED: 07-10-2010
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Hypothyroidism decreases energy expenditure and combustion of fuels, but the reported effects on lipid metabolism and insulin sensitivity are divergent and there is a lack of studies assessing rates of lipolysis and lipid oxidation. The present study was conducted to test the hypotheses that hypothyroidism decreases lipolysis, blood concentrations of free fatty acid, lipid oxidation, and insulin sensitivity.
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Reduced expression of uncoupling protein 2 in adipose tissue in patients with hypothyroidism.
J. Clin. Endocrinol. Metab.
PUBLISHED: 04-28-2010
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Thyroid disease is associated with major metabolic changes, comprising changes in lipid metabolism. Thyroid hormones have previously been shown to increase UCP2 mRNA expression in fat biopsies from hyperthyroid patients, but data from hypothyroid patients have so far not been reported.
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Recurrence of hyperprolactinemia after withdrawal of dopamine agonists: systematic review and meta-analysis.
J. Clin. Endocrinol. Metab.
PUBLISHED: 10-30-2009
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Dopamine agonists are the treatment of choice for prolactinomas and symptomatic idiopathic hyperprolactinemia. However, the optimal treatment strategy and treatment duration is not clear in all details.
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Effects of GH in human muscle and fat.
Pediatr. Nephrol.
PUBLISHED: 08-16-2009
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Skeletal muscle is the major constituent of lean body mass and a major determinant of energy expenditure both at rest and during physical activity. Growth hormone, in turn, influences muscle mass as well as energy expenditure. Growth hormone substitution in adults increases muscle mass by 5-10%, but part of the effect is attributed to rehydration rather than protein accretion. In addition, GH regulates substrate metabolism in muscle and in particular antagonizes insulin-stimulated glucose disposal. This effect is linked to increased free fatty acid (FFA) flux but the molecular mechanisms remain unclear. During fasting, GH-induced insulin resistance may be favorable by reducing the demand of gluconeogenesis from protein. But in the postprandial phase, GH exposure may compromise glucose tolerance via the same mechanisms. Understanding the mechanisms whereby GH antagonizes insulin-stimulated glucose disposal in muscle is an important future research field with implications for a variety of clinical conditions ranging from malnutrition to obesity and type 2 diabetes.
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Free fatty acids inhibit growth hormone/signal transducer and activator of transcription-5 signaling in human muscle: a potential feedback mechanism.
J. Clin. Endocrinol. Metab.
PUBLISHED: 03-10-2009
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Stimulation of lipolysis, leading to increased blood concentrations of free fatty acids (FFAs), is a primary effect of GH and phosphorylation of intracellular signal transducer and activator of transcription (STAT)-5 is a primary mediator of the effects of GH.
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Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects.
Endocr. Rev.
PUBLISHED: 02-24-2009
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In evolutionary terms, GH and intracellular STAT 5 signaling is a very old regulatory system. Whereas insulin dominates periprandially, GH may be viewed as the primary anabolic hormone during stress and fasting. GH exerts anabolic effects directly and through stimulation of IGF-I, insulin, and free fatty acids (FFA). When subjects are well nourished, the GH-induced stimulation of IGF-I and insulin is important for anabolic storage and growth of lean body mass (LBM), adipose tissue, and glycogen reserves. During fasting and other catabolic states, GH predominantly stimulates the release and oxidation of FFA, which leads to decreased glucose and protein oxidation and preservation of LBM and glycogen stores. The most prominent metabolic effect of GH is a marked increase in lipolysis and FFA levels. In the basal state, the effects of GH on protein metabolism are modest and include increased protein synthesis and decreased breakdown at the whole body level and in muscle together with decreased amino acid degradation/oxidation and decreased hepatic urea formation. During fasting and stress, the effects of GH on protein metabolism become more pronounced; lack of GH during fasting increases protein loss and urea production rates by approximately 50%, with a similar increase in muscle protein breakdown. GH is a counterregulatory hormone that antagonizes the hepatic and peripheral effects of insulin on glucose metabolism via mechanisms involving the concomitant increase in FFA flux and uptake. This ability of GH to induce insulin resistance is significant for the defense against hypoglycemia, for the development of "stress" diabetes during fasting and inflammatory illness, and perhaps for the "Dawn" phenomenon (the increase in insulin requirements in the early morning hours). Adult patients with GH deficiency are insulin resistant-probably related to increased adiposity, reduced LBM, and impaired physical performance-which temporarily worsens when GH treatment is initiated. Conversely, despite increased LBM and decreased fat mass, patients with acromegaly are consistently insulin resistant and become more sensitive after appropriate treatment.
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High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition.
Diabetes
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Obesity, diabetes, hypertension, and hyperlipidemia constitute risk factors for morbidity and premature mortality. Based on animal and in vitro studies, resveratrol reverts these risk factors via stimulation of silent mating type information regulation 2 homolog 1 (SIRT1), but data in human subjects are scarce. The objective of this study was to examine the metabolic effects of high-dose resveratrol in obese human subjects. In a randomized, placebo-controlled, double-blinded, and parallel-group design, 24 obese but otherwise healthy men were randomly assigned to 4 weeks of resveratrol or placebo treatment. Extensive metabolic examinations including assessment of glucose turnover and insulin sensitivity (hyperinsulinemic euglycemic clamp) were performed before and after the treatment. Insulin sensitivity, the primary outcome measure, deteriorated insignificantly in both groups. Endogenous glucose production and the turnover and oxidation rates of glucose remained unchanged. Resveratrol supplementation also had no effect on blood pressure; resting energy expenditure; oxidation rates of lipid; ectopic or visceral fat content; or inflammatory and metabolic biomarkers. The lack of effect disagrees with persuasive data obtained from rodent models and raises doubt about the justification of resveratrol as a human nutritional supplement in metabolic disorders.
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Local administration of growth hormone stimulates tendon collagen synthesis in elderly men.
J. Appl. Physiol.
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Tendon collagen content and circulating growth hormone (GH) are reduced in elderly. In a placebo-controlled, double-blinded study, we examined if local injections of rhGH enhance collagen synthesis in healthy elderly men (61 ± 1 yr). Two injections of rhGH or saline (control) were injected into each of the patients patellar tendons, respectively. Subsequently, tendon collagen fractional synthesis rate (FSR) and an indirect marker of type I collagen synthesis (PINP) were measured. Within the first 6 h after the last injections, a tendency towards a higher tendon collagen FSR was observed in 10 out of 12 subjects (P = 0.08). Similarly, PINP was higher 3-4 h after the last GH injection (P = 0.05). Serum IGF-I did not change from baseline, whereas peritendinous bioactive IGF-I was higher in the GH leg vs. control (P = 0.05). In conclusion, local injections of rhGH increase tendon collagen synthesis in humans, either directly or indirectly by increasing local bioactive IGF-I.
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[Diagnostics and new treatment methods of syndrome of inappropriate antidiuretic hormone secretion (SIADH)].
Ugeskr. Laeg.
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New treatment methods of syndrome of inappropriate antidiuretic hormone secretion (SIADH) has emerged with the oral vasopressin V2-receptor antagonist (VV2RA) tolvaptan, but its therapeutic window remains to be defined. We present the scientific data and describe treatment possibilities of SIADH while raising the questions: "Does the present evidence enable us to identify who to treat with VV2RAs?" and "is VV2RAs justified as first-line treatment?".
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Evaluation of functional erythropoietin receptor status in skeletal muscle in vivo: acute and prolonged studies in healthy human subjects.
PLoS ONE
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Erythropoietin receptors have been identified in human skeletal muscle tissue, but downstream signal transduction has not been investigated. We therefore studied in vivo effects of systemic erythropoietin exposure in human skeletal muscle.
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Fat content in liver and skeletal muscle changes in a reciprocal manner in patients with acromegaly during combination therapy with a somatostatin analog and a GH receptor antagonist: a randomized clinical trial.
J. Clin. Endocrinol. Metab.
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Pegvisomant is a GH antagonist, which is used for the treatment of acromegalic patients. It effectively blocks the hepatic and peripheral effects of GH, but transient elevations in circulating liver enzymes of unknown pathogenesis may occur, which seems to be more prevalent when the treatment is combined with a somatostatin analog (SA). Accumulation of intrahepatic lipid is a known cause of elevated liver enzymes, and there is evidence to suggest that GH impacts lipid content in liver and skeletal muscle.
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Erythropoietin administration acutely stimulates resting energy expenditure in healthy young men.
J. Appl. Physiol.
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Treatment with recombinant human erythropoietin (rHuEpo) improves insulin sensitivity in patients with end-stage renal disease, and animal studies indicate that Epo increases fat oxidation. However, the metabolic effects of rHuEpo have never been experimentally studied in healthy humans. The aim was to investigate the effects of an acute rHuEpo bolus on substrate metabolism and insulin sensitivity in healthy young men. Ten healthy young men were studied in a single-blinded, randomized crossover design with a 2-wk washout period receiving 400 IU/kg rHuEpo or placebo. Substrate metabolism was evaluated by indirect calorimetry and tracer infusions, and insulin sensitivity by a hyperinsulinemic euglycemic clamp; and PCR and Western blotting measured protein expression and content, respectively. Resting energy expenditure (REE) increased significantly after rHuEpo [basal: 1,863.3 ± 67.2 (kcal/day) (placebo) vs. 2,041.6 ± 81.2 (rHuEpo), P < 0.001; clamp: 1,903.9 ± 68.3 (placebo) vs. 2,015.7 ± 114.4 (rHuEpo), P = 0.03], but the increase could not be explained by changes in mRNA levels of uncoupling protein 2 or 3. Fat oxidation in the basal state tended to be higher after rHuEpo but could not be explained by changes in mRNA levels of CPT1 and PPAR? or AMPK and ACC protein phosphorylation. Insulin-stimulated glucose disposal, glucose metabolism, and whole body and forearm protein metabolism did not change significantly in response to rHuEpo. In conclusion, a single injection of rHuEpo acutely increases REE in healthy human subjects. This calorigenic effect is not accompanied by distinct alterations in the pattern of substrate metabolism or insulin sensitivity.
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