Whole body metabolic effects of prolonged endurance training in combination with erythropoietin treatment in humans: a randomized placebo controlled trial

Christensen, Britt; Nellemann, Birgitte; Larsen, Mads S.; Thams, Line; Sieljacks, Peter; Vestergaard, P; Bibby, Bo Martin; Vissing, Kristian; Stødkilde-Jørgensen, Hans; Pedersen, Steen B.; Møller, Niels; Nielsén, Sören; Jessen, Niels; Jørgensen, Jens Otto Lunde

doi:10.1152/ajpendo.00269.2013

Cited by 33 publications

(71 citation statements)

References 58 publications

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“…Previous studies have reported that there may be an association between EPO levels and hypoglycemia, which suggests a potential protective effect of EPO in the treatment of diabetes (1)(2)(3)19,20). The present study demonstrated that treatment with EPO (300 U/kg, three times a week for 4 weeks) was effective in reducing FBG and improving insulin resistance in high-fat diet/low dose STZ-induced experimental diabetic rats.…”

Section: Discussionsupporting

confidence: 70%

Erythropoietin improves glucose metabolism and pancreatic β-cell damage in experimental diabetic rats

et al. 2015

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Abstract. Previous studies have implicated erythropoietin (EPO) signaling in the regulation of glucose metabolism. Whether EPO can be used treat diabetes and the underlying mechanism remain to be elucidated. The present study aimed to investigate whether EPO affects glucose metabolism, and the underlying mechanisms, in experimental diabetic rats. The effects of EPO (300 U/kg three times a week for 4 weeks) on glucose metabolism, hematopoietic function, blood selenium content and the ultrastructure of pancreatic β-cells were investigated in low dose (25 mg/kg body weight) streptozotocin-induced experimental diabetic rats provided with a high-fat diet. The results demonstrated that EPO significantly decreased the fasting blood glucose, the area under the curve of the oral glucose tolerance and insulin tolerance tests and L-alanine gluconeogenesis. Ultrastructural examination of the pancreatic islets revealed that EPO prevented the dysfunction of pancreatic β-cells in experimental diabetic rats, ameliorated cytoplasmic vacuolation and fragmentation of mitochondria, and increased the number of secretory granules. EPO administration increased the activities of superoxide dismutase and glutathione peroxidase, and decreased the level of malondialdehyde. Additionally, EPO increased blood selenium in the diabetic rats and produced a hematopoietic effect. These results indicated that EPO modulated glucose metabolism and improved pancreatic β-cells damage by increasing anti-oxidation. The detailed mechanisms underlying these effects require further investigation.

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Section: Discussionsupporting

confidence: 70%

Erythropoietin improves glucose metabolism and pancreatic β-cell damage in experimental diabetic rats

et al. 2015

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“…Endurance training induces physiological changes that can improve exercise performance in terms of haematopoietic induction, which increases O 2 transport to muscles. This type of training and EPO both stimulate a shift in skeletal muscle, from a fast glycolytic to a slower oxidative phenotype, by inducing mitochondrial biogenesis, which also improves aerobic exercise capacity (28,31,32). Haemoglobin concentration rises because of increased erythrocytes mass, and decreased plasma volume during exercise (10).…”

Section: Physical Activity and Blood Dopingmentioning

confidence: 99%

“…Therefore, in 1990 the International Olympic Committee prohibited rHuEPO use in athletes (26,35 (33). Apart from EPO, other agents are also misused to stimulate erythropoiesis, such as HIFs, even though they induce expression of more than 200 genes, beside EPO gene, or cobalt, although it has serious toxic effects, or prolyl hydroxylase inhibitors, HCP inhibitors, EPO mimetic peptides and recombinant fusion proteins of EPO (26,31,33). Several hormones may also stimulate EPO production, like thyroid hormone, growth hormone, testosterone, angiotensin II, prostanoids (29,33).…”

Section: Physical Activity and Blood Dopingmentioning

confidence: 99%

Erythropoietin between therapy and doping : Two sides of the same coin

Ostojić¹,

Trbojević-Stanković²,

Nešić³

2016

Medicinski podmladak

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SažetakEritropoetin je hormon koji se kod odraslih stvara pretežno u bubrezima, a u manjoj meri i u jetri, kao odgovor na hipoksiju. Primarno stimuliše eritropoezu u koštanoj srži i deluje antiapoptozno, antiinflamatorno i citoprotektivno. Stvara se lokalno i deluje i u mnogim drugim, nehematopoetskim tkivima, ispoljavajući u njima i svoj proangiogeni potencijal. Eritropoetin se vezuje za citokinski receptor koji eksprimiraju ciljne ćelije, prekursori eritrocita, ali i neuroni, ćelije glije, endotelne ćelije, kardiomiociti, miociti i dr. Pronalaskom sintetskih formi eritropoetina, krajem osamdesetih godina prošlog veka, značajno je unapređeno lečenje bolesnika sa anemijom usled hroničnih bolesti, najčešće renalne insuficijencije. Anemija u hroničnoj bubrežnoj insuficijenciji je multifaktorska, ali u najvećoj meri posledica manjka eritropoetina. Do sada su razvijene tri generacije stimulatora eritropoeze, koji se razlikuju u ugljenohidratnom delu, veličini, polu-životu u cirkulaciji, načinu primene i dozi. I pored značajno poboljšanog kvaliteta života anemičnih bolesnika, postoje ozbiljni, potencijalno ugrožavajući efekti ove terapije. Sinteza rekombinovanog humanog eritropoetina, s druge strane, otvorila je nove mogućnosti i za zloupotrebu u sportu, u domenu krvnog dopinga. Davanje eritropoetina zdravim sportistima podiže njihov aerobni kapacitet i poboljšava izdržljivost i rezultate, posebno u aerobnim disciplinama. Time se ozbiljno narušava sportski duh, ali i ozbiljno ugrožava zdravlje sportista. U upotrebi su različiti testovi za otkrivanje nedozvoljenih supstanci, ali je uspeh ovih metoda još uvek ograničen. Uporedo se stalno razvijaju i pronalaze drugi načini zloupotrebe u sportu, poput novijih, različitih modela genetskog dopinga. Zbog svega navedenog razvoj novih modela antidoping testova i bolja zdravstvena kontrola sportista i dalje predstavljaju veliki izazov. Ključne reči: eritropoetin, eritropoeza, anemija, sportisti, doping AbstractErythropoietin is a hormone that promotes the formation of red blood cells by the bone marrow. In adults it is mainly produced by the kidneys as a response to hypoxia. Besides its main role, it also acts as antiapoptotic, anti-inflammatory and cytoprotective agent. Furthermore, it is produced in many non-hematopoietic tissues where it acts locally, stimulating angiogenesis. Erythropoietin binds cytokine receptors on target cells, such as erythrocyte precursor cells, neurons, glial and endothelial cells, cardiomyocytes, myocytes etc. The discovery of synthetic erythropoietin forms, in the late eighties of the last century, has significantly improved treatment outcome of patients with anaemia related to chronic diseases, especially chronic renal failure. Renal anaemia is multifactorial, but predominantly a consequence of erythropoietin deficiency. Today, three generations of erythropoiesis stimulating agents are available, differing in glycosylation pattern, molecular size, half-life and modes of administration and dosage. In anaemic patients this therapy significantly imp...

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“…This study examined VLDL-TG and FFA (palmitate) kinetics and oxidation rates of the participants in the C and Tr subgroups with no injections of erythropoiesisstimulating agent. Inclusion criteria (29) required that all participants were untrained, with a VO 2 max !50 ml/kg per min. Additionally, all were normotensive, nonsmokers, used no medication, and had a normal blood count, lipid profile, fasting plasma glucose, HbA1c, and a normal electrocardiogram.…”

Section: Subjectsmentioning

confidence: 99%

“…A detailed description of the study design has been reported elsewhere (29). In brief, in a randomized, paired design, subjects were allocated to a C group (nZ9) or a Tr group (nZ10).…”

Section: Experimental Designmentioning

confidence: 99%

Ten weeks of aerobic training does not result in persistent changes in VLDL triglyceride turnover or oxidation in healthy men

Nellemann

Christensen

Vissing

et al. 2014

European Journal of Endocrinology

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Objective: 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. Design: The aim was to investigate long-term effects of training by direct assessments of VLDL-TG and palmitate kinetics and oxidation in healthy lean men (nZ9) at rest, before and after a 10-week training program, compared with a non-training control group (nZ9). Methods: VLDL-TG kinetics were assessed by a primed constant infusion of [1-14 C]VLDL-TG, and VLDL-TG oxidation by specific activity ( 14 CO 2 ) in expired air. The metabolic study days were placed 60-72 h after the last exercise bout.Results: Palmitate kinetics and oxidation were assessed by a 2 h constant infusion of [9,10-3 H]palmitate. In the training group (nZ9), maximal oxygen uptake increased significantly by z20% (P!0.05), and the insulin sensitivity (assessed by the hyperinsulinemic-euglycemic clamp) improved significantly (P!0.05). Despite these metabolic improvements, no changes were observed in VLDL-TG secretion, clearance, or oxidation or in palmitate kinetics. Conclusion:We conclude that 10 weeks of exercise training did not induce changes in VLDL-TG and palmitate kinetics in healthy lean men.

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Whole body metabolic effects of prolonged endurance training in combination with erythropoietin treatment in humans: a randomized placebo controlled trial

Cited by 33 publications

References 58 publications

Erythropoietin improves glucose metabolism and pancreatic β-cell damage in experimental diabetic rats

Erythropoietin improves glucose metabolism and pancreatic β-cell damage in experimental diabetic rats

Erythropoietin between therapy and doping : Two sides of the same coin

Ten weeks of aerobic training does not result in persistent changes in VLDL triglyceride turnover or oxidation in healthy men

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