{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:42:41Z","timestamp":1791412961928,"version":"4.3.3"},"reference-count":57,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,2,15]],"date-time":"2016-02-15T00:00:00Z","timestamp":1455494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cancer is considered the second leading cause of death in the world, and for the treatment of this disease, pharmacological intervention strategies are frequently based on chemotherapy. Doxorubicin (DOX) is one of the most widely used chemotherapeutic agents in clinical practice for treating a number of solid tumours. The treatment with DOX mimics some effects of cancer cachexia, such as anorexia, asthenia, decreases in fat and skeletal muscle mass and fatigue. We observed that treatment with DOX increased the systemic insulin resistance and caused a massive increase in glucose levels in serum. Skeletal muscle is a major tissue responsible for glucose uptake, and the positive role of AMPk protein (AMP\u2010activated protein kinase) in GLUT\u20104 (Glucose Transporter type 4) translocation, is well established. With this, our aim was to assess the insulin sensitivity after treatment with DOX and involvement of AMPk signalling in skeletal muscle in this process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used Wistar rats which received a single dose of doxorubicin (DOX group) or saline (CT group) intraperitoneally at a dose of 15\u2009mg\/kg b.w. The expression of proteins involved in insulin sensitivity, glucose uptake, inflammation, and activity of electron transport chain was assessed in extensor digitorum longus muscle, as well as the histological evaluation.\n                      <jats:italic>In vitro<\/jats:italic>\n                      assays were performed in L6 myocytes to assess glucose uptake after treatment with DOX. Agonist of AMPk [5\u2010aminoimidazole\u20104\u2010carboxamide (AICAR)] and the antioxidant n\u2010acetyl cysteine were used in L6 cells to evaluate its effect on glucose uptake and cell viability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The animals showed a significant insulin resistance, hyperglycaemia, and hyperinsulinemia. A decrease in the expression of AMKP and GLUT\u20104 was observed in the extensor digitorum longus muscle. Also in L6 cells, DOX leads to a decrease in glucose uptake, which is reversed with AICAR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      DOX leads to conditions similar to cachexia, with severe glucose intolerance both\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      . The decrease of AMPk activity of the protein is modulated negatively with DOX, and treatment with agonist of AMPk (AICAR) has proved to be a possible therapeutic target, which is able to recover glucose sensitivity in skeletal muscle.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12104","type":"journal-article","created":{"date-parts":[[2016,2,15]],"date-time":"2016-02-15T01:52:45Z","timestamp":1455501165000},"page":"615-625","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":117,"title":["Doxorubicin caused severe hyperglycaemia and insulin resistance, mediated by inhibition in AMPk signalling in skeletal muscle"],"prefix":"10.1002","volume":"7","author":[{"given":"Edson Alves","family":"de Lima Junior","sequence":"first","affiliation":[{"name":"Departamento de Biologia Celular e do Desenvolvimento Instituto de Ci\u00eancias Biom\u00e9dicas I Avenida Lineu Prestes 1524, Cidade Universit\u00e1ria 05508\u2010900 S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex Shimura","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia e Biof\u00edsica, Instituto de Ci\u00eancias Biom\u00e9dicas Universidade de S\u00e3o Paulo S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Duarte","family":"Pimentel","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00e3o em Nutri\u00e7\u00e3o Cl\u00ednica e Esportiva(Labince), Faculdade de Nutri\u00e7\u00e3o (FANUT) Universidade Federal de Goi\u00e1s (UFG) Goi\u00e2nia Goi\u00e1s Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00eds G. O.","family":"De Sousa","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Physiology and Behavior University of California Davis Davis CA 95616 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronaldo Vagner T","family":"Santos","sequence":"additional","affiliation":[{"name":"Departamento de Bioci\u00eancias UNIFESP S\u00e3o Paulo SP Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinara Ludvig","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Fisiopatologia Experimental Universidade do Extremo Sul Catarinense, Av. Universit\u00e1ria, 1105 Crici\u00fama88806\u2010000SC Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio Luiz","family":"Streck","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Fisiopatologia Experimental Universidade do Extremo Sul Catarinense, Av. 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