title: Chronic erythropoietin treatment improves diet-induced glucose intolerance in rats.
abstract: Erythropoietin (EPO) ameliorates glucose metabolism through mechanisms not fully understood. In this study, we investigated the effect of EPO on glucose metabolism and insulin signaling in skeletal muscle. A 2-week EPO treatment of rats fed with a high-fat diet (HFD) improved fasting glucose levels and glucose tolerance, without altering total body weight or retroperitoneal fat mass. Concomitantly, EPO partially rescued insulin-stimulated AKT activation, reduced markers of oxidative stress, and restored heat-shock protein 72 expression in soleus muscles from HFD-fed rats. Incubation of skeletal muscle cell cultures with EPO failed to induce AKT phosphorylation and had no effect on glucose uptake or glycogen synthesis. We found that the EPO receptor gene was expressed in myotubes, but was undetectable in soleus. Together, our results indicate that EPO treatment improves glucose tolerance but does not directly activate the phosphorylation of AKT in muscle cells. We propose that the reduced systemic inflammation or oxidative stress that we observed after treatment with EPO could contribute to the improvement of whole-body glucose metabolism.
authors.affiliation: Exercise Health and Performance Faculty of Health Sciences, and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia Faculty of Health and Medical Sciences The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Department of Neuroscience and Pharmacology Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark School of Medicine and Pharmacology Royal Perth Hospital, The University of Western Australia, Perth, Western Australia, Australia UMR CNRS 9214 U1046 INSERM Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Montpellier, France Physiology Department CHU Arnaud de Villeneuve, Montpellier, France Department of Endocrinology Sydney Medical School, Royal Prince Alfred Hospital, University of Sydney, Camperdown, New South Wales, Australia Inflammation and Infection Research School of Medical Sciences, UNSW Australia, Sydney, New South Wales, Australia corinne.caillaud@sydney.edu.au barres@sund.ku.dk.
authors.forename: Corinne
authors.initials: C
authors.lastname: Caillaud
authors.affiliation: Exercise Health and Performance Faculty of Health Sciences, and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia Faculty of Health and Medical Sciences The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Department of Neuroscience and Pharmacology Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark School of Medicine and Pharmacology Royal Perth Hospital, The University of Western Australia, Perth, Western Australia, Australia UMR CNRS 9214 U1046 INSERM Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Montpellier, France Physiology Department CHU Arnaud de Villeneuve, Montpellier, France Department of Endocrinology Sydney Medical School, Royal Prince Alfred Hospital, University of Sydney, Camperdown, New South Wales, Australia Inflammation and Infection Research School of Medical Sciences, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: Mie
authors.initials: M
authors.lastname: Mechta
authors.affiliation: Exercise Health and Performance Faculty of Health Sciences, and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia Faculty of Health and Medical Sciences The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Department of Neuroscience and Pharmacology Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark School of Medicine and Pharmacology Royal Perth Hospital, The University of Western Australia, Perth, Western Australia, Australia UMR CNRS 9214 U1046 INSERM Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Montpellier, France Physiology Department CHU Arnaud de Villeneuve, Montpellier, France Department of Endocrinology Sydney Medical School, Royal Prince Alfred Hospital, University of Sydney, Camperdown, New South Wales, Australia Inflammation and Infection Research School of Medical Sciences, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: Heidi
authors.initials: H
authors.lastname: Ainge
authors.affiliation: Exercise Health and Performance Faculty of Health Sciences, and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia Faculty of Health and Medical Sciences The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Department of Neuroscience and Pharmacology Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark School of Medicine and Pharmacology Royal Perth Hospital, The University of Western Australia, Perth, Western Australia, Australia UMR CNRS 9214 U1046 INSERM Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Montpellier, France Physiology Department CHU Arnaud de Villeneuve, Montpellier, France Department of Endocrinology Sydney Medical School, Royal Prince Alfred Hospital, University of Sydney, Camperdown, New South Wales, Australia Inflammation and Infection Research School of Medical Sciences, UNSW Australia, Sydney, New South Wales, Australia Exercise Health and Performance Faculty of Health Sciences, and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia Faculty of Health and Medical Sciences The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Department of Neuroscience and Pharmacology Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark School of Medicine and Pharmacology Royal Perth Hospital, The University of Western Australia, Perth, Western Australia, Australia UMR CNRS 9214 U1046 INSERM Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Montpellier, France Physiology Department CHU Arnaud de Villeneuve, Montpellier, France Department of Endocrinology Sydney Medical School, Royal Prince Alfred Hospital, University of Sydney, Camperdown, New South Wales, Australia Inflammation and Infection Research School of Medical Sciences, UNSW Australia, Sydney, N
authors.forename: Andreas N
authors.initials: AN
authors.lastname: Madsen
authors.affiliation: Exercise Health and Performance Faculty of Health Sciences, and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia Faculty of Health and Medical Sciences The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Department of Neuroscience and Pharmacology Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark School of Medicine and Pharmacology Royal Perth Hospital, The University of Western Australia, Perth, Western Australia, Australia UMR CNRS 9214 U1046 INSERM Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Montpellier, France Physiology Department CHU Arnaud de Villeneuve, Montpellier, France Department of Endocrinology Sydney Medical School, Royal Prince Alfred Hospital, University of Sydney, Camperdown, New South Wales, Australia Inflammation and Infection Research School of Medical Sciences, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ruell
authors.affiliation: Exercise Health and Performance Faculty of Health Sciences, and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia Faculty of Health and Medical Sciences The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Department of Neuroscience and Pharmacology Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark School of Medicine and Pharmacology Royal Perth Hospital, The University of Western Australia, Perth, Western Australia, Australia UMR CNRS 9214 U1046 INSERM Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Montpellier, France Physiology Department CHU Arnaud de Villeneuve, Montpellier, France Department of Endocrinology Sydney Medical School, Royal Prince Alfred Hospital, University of Sydney, Camperdown, New South Wales, Australia Inflammation and Infection Research School of Medical Sciences, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: Emilie
authors.initials: E
authors.lastname: Mas
authors.affiliation: Exercise Health and Performance Faculty of Health Sciences, and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia Faculty of Health and Medical Sciences The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Department of Neuroscience and Pharmacology Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark School of Medicine and Pharmacology Royal Perth Hospital, The University of Western Australia, Perth, Western Australia, Australia UMR CNRS 9214 U1046 INSERM Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Montpellier, France Physiology Department CHU Arnaud de Villeneuve, Montpellier, France Department of Endocrinology Sydney Medical School, Royal Prince Alfred Hospital, University of Sydney, Camperdown, New South Wales, Australia Inflammation and Infection Research School of Medical Sciences, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: Catherine
authors.initials: C
authors.lastname: Bisbal
authors.affiliation: Exercise Health and Performance Faculty of Health Sciences, and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia Faculty of Health and Medical Sciences The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Department of Neuroscience and Pharmacology Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark School of Medicine and Pharmacology Royal Perth Hospital, The University of Western Australia, Perth, Western Australia, Australia UMR CNRS 9214 U1046 INSERM Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Montpellier, France Physiology Department CHU Arnaud de Villeneuve, Montpellier, France Department of Endocrinology Sydney Medical School, Royal Prince Alfred Hospital, University of Sydney, Camperdown, New South Wales, Australia Inflammation and Infection Research School of Medical Sciences, UNSW Australia, Sydney, New South Wales, Australia Exercise Health and Performance Faculty of Health Sciences, and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia Faculty of Health and Medical Sciences The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Department of Neuroscience and Pharmacology Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark School of Medicine and Pharmacology Royal Perth Hospital, The University of Western Australia, Perth, Western Australia, Australia UMR CNRS 9214 U1046 INSERM Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Montpellier, France Physiology Department CHU Arnaud de Villeneuve, Montpellier, France Department of Endocrinology Sydney Medical School, Royal Prince Alfred Hospital, University of Sydney, Camperdown, New South Wales, Australia Inflammation and Infection Research School of Medical Sciences, UNSW Australia, Sydney, N
authors.forename: Jacques
authors.initials: J
authors.lastname: Mercier
authors.affiliation: Exercise Health and Performance Faculty of Health Sciences, and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia Faculty of Health and Medical Sciences The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Department of Neuroscience and Pharmacology Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark School of Medicine and Pharmacology Royal Perth Hospital, The University of Western Australia, Perth, Western Australia, Australia UMR CNRS 9214 U1046 INSERM Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Montpellier, France Physiology Department CHU Arnaud de Villeneuve, Montpellier, France Department of Endocrinology Sydney Medical School, Royal Prince Alfred Hospital, University of Sydney, Camperdown, New South Wales, Australia Inflammation and Infection Research School of Medical Sciences, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Twigg
authors.affiliation: Exercise Health and Performance Faculty of Health Sciences, and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia Faculty of Health and Medical Sciences The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Department of Neuroscience and Pharmacology Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark School of Medicine and Pharmacology Royal Perth Hospital, The University of Western Australia, Perth, Western Australia, Australia UMR CNRS 9214 U1046 INSERM Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Montpellier, France Physiology Department CHU Arnaud de Villeneuve, Montpellier, France Department of Endocrinology Sydney Medical School, Royal Prince Alfred Hospital, University of Sydney, Camperdown, New South Wales, Australia Inflammation and Infection Research School of Medical Sciences, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Mori
authors.affiliation: Exercise Health and Performance Faculty of Health Sciences, and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia Faculty of Health and Medical Sciences The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Department of Neuroscience and Pharmacology Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark School of Medicine and Pharmacology Royal Perth Hospital, The University of Western Australia, Perth, Western Australia, Australia UMR CNRS 9214 U1046 INSERM Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Montpellier, France Physiology Department CHU Arnaud de Villeneuve, Montpellier, France Department of Endocrinology Sydney Medical School, Royal Prince Alfred Hospital, University of Sydney, Camperdown, New South Wales, Australia Inflammation and Infection Research School of Medical Sciences, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Simar
authors.affiliation: Exercise Health and Performance Faculty of Health Sciences, and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia Faculty of Health and Medical Sciences The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Department of Neuroscience and Pharmacology Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark School of Medicine and Pharmacology Royal Perth Hospital, The University of Western Australia, Perth, Western Australia, Australia UMR CNRS 9214 U1046 INSERM Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Montpellier, France Physiology Department CHU Arnaud de Villeneuve, Montpellier, France Department of Endocrinology Sydney Medical School, Royal Prince Alfred Hospital, University of Sydney, Camperdown, New South Wales, Australia Inflammation and Infection Research School of Medical Sciences, UNSW Australia, Sydney, New South Wales, Australia corinne.caillaud@sydney.edu.au barres@sund.ku.dk.
authors.forename: Romain
authors.initials: R
authors.lastname: Barrès
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D004921:Erythropoietin / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism; D018384:Oxidative Stress; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism
chemical_list: D050884:HSP72 Heat-Shock Proteins; D007328:Insulin; D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose
keywords: glucose metabolism; high-fat diet; myotubes; skeletal muscle