Effects of Erythropoietin on Glucose Metabolism
ABSTRACT We purposed to determine the impact of erythropoietin on altering glucose metabolism in the settings of in vitro and in vivo experiments. The acute effect of erythropoietin on lowering blood glucose levels was studied in animal experiments. In [³H]-deoxy-D-glucose isotope studies we measured glucose uptake with insulin and erythropoietin using 3T3-L1 cells cultured under normal or high glucose conditions. Altered activation of Akt and ERK pathways was evaluated in immunoblot analyses. Immunocytochemistry was conducted to determine the glucose transporter 4 translocation to the plasma membrane. Addition of erythropoietin significantly lowered blood glucose levels in vivo in rats. The glucose uptake was markedly increased by erythropoietin treatment (at concentrations 0.15, 0.3, and 0.625 ng/ml) in adipocytes grown in high glucose medium (p<0.05), but it remained unaltered in cells under normal glucose conditions. Significant increase of phosphorylation of ERK and Akt was detected due to erythropoietin (p<0.05). Co-administration of erythropoietin and insulin resulted in higher phosphorylation of Akt and [³H]-deoxy-D-glucose uptake in adipocytes than insulin treatment alone. We found that erythropoietin induced the trafficking of glucose transporter 4 to the plasma membrane. Our data showed that erythropoietin significantly decreased blood glucose levels both in vivo and in vitro, in part, by increasing glucose uptake via the activation of Akt pathway. Preliminary data revealed that adipocytes most likely exhibit a specific receptor for erythropoietin.
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ABSTRACT: Discuss the influence of rHuEPO on physical performance, as well as the adverse effects of this practice, exposing results from experimental and clinical studies.Methods Were selected articles published in the basis, PubMed and SciELO databases, in the period 1985‐2013, using the following keywords eritropoetina/erythropoietin, desempenho atlético/athletic performance, resistência física/physical endurance, efeitos adversos/adverse effects e doping nos esportes/doping in sports.ResultsAll articles (n = 10) related to the influence of treatment with rHuEPO on sports performance, found improvement in the variables of maximal oxygen uptake (VO2max) and time to exhaustion in humans, using different protocols dosages between 50 to 60 IU/kg during the first weeks with reduced throughout treatment. Among the most common adverse effects are the thrombovascular accidents, iron deficiency and hypertension.Conclusion Treatment with rHuEPO doses and at different periods, can enhance physical performance in humans, because of the different generated effects, including increased O2 transport, reduction of blood lactate concentrations, increased concentrations of free fatty acids in the blood and muscle glycogen.Revista Andaluza de Medicina del Deporte 11/2014; DOI:10.1016/j.ramd.2014.03.001
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ABSTRACT: Erythropoietin (EPO), the required cytokine for promoting the proliferation and differentiation of erythroid cells to stimulate erythropoiesis, has been reported to act as a pleiotropic cytokine beyond hematopoietic system. The various activities of EPO are determined by the widespread distribution of its cell surface EPO receptor (EpoR) in multiple tissues including endothelial, neural, myoblasts, adipocytes and other cell types. EPO activity has been linked to angiogenesis, neuroprotection, cardioprotection, stress protection, anti-inflammation and especially the energy metabolism regulation that is recently revealed. The investigations of EPO activity in animals and the expression analysis of EpoR provide more insights on the potential of EPO in regulating energy metabolism and homeostasis. The findings of crosstalk between EPO and some important energy sensors and the regulation of EPO in the cellular respiration and mitochondrial function further provide molecular mechanisms for EPO activity in metabolic activity regulation. In this review, we will summarize the roles of EPO in energy metabolism regulation and the activity of EPO in tissues that are tightly associated with energy metabolism. We will also discuss the effects of EPO in regulating oxidative metabolism and mitochondrial function, the interactions between EPO and important energy regulation factors, and the protective role of EPO from stresses that are related to metabolism, providing a brief overview of previously less appreciated EPO biological function in energy metabolism and homeostasis.International journal of biological sciences 01/2014; 10(8):921-939. DOI:10.7150/ijbs.9518 · 4.37 Impact Factor
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ABSTRACT: The growing prevalence of obesity and diabetes necessitate a better understanding of the role of adipocyte biology in metabolism. Increasingly, erythropoietin (EPO) has been shown to have extra-erythropoietic and cytoprotective roles. Exogenous administration has recently been shown to have beneficial effects on obesity and diabetes in mouse models and EPO can modulate adipogenesis and insulin signalling in 3T3-L1 adipocytes. However, its physiological role in adipocytes has not been identified. Using male and female mice with adipose tissue-specific knockdown of the erythropoietin receptor (EpoR), we determine that adipocyte EPO signalling is not essential for maintenance of energy homeostasis, or glucose metabolism. Adipose tissue-specific disruption of EpoR did not alter adipose tissue expansion, adipocyte morphology, insulin resistance, inflammation or angiogenesis in vivo. In contrast to the pharmacological effects of EPO, we demonstrate that EPO signalling at physiological levels is not essential for adipose tissue regulation of metabolism.Endocrinology 07/2013; 154(10). DOI:10.1210/en.2013-1113 · 4.64 Impact Factor