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Accumulation of advanced glycation end\u2010products (\n                    <jats:styled-content style=\"fixed-case\">AGEs<\/jats:styled-content>\n                    ), known to play a role in diabetic complications, has been identified in ageing human skeletal muscles. However, the role of\n                    <jats:styled-content style=\"fixed-case\">AGEs<\/jats:styled-content>\n                    in diabetic myopathy remains unclear. Here, we investigated the effects of\n                    <jats:styled-content style=\"fixed-case\">AGEs<\/jats:styled-content>\n                    on myogenic differentiation and muscle atrophy\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    . We also evaluated the therapeutic potential of alagebrium chloride (Ala\u2010Cl), an inhibitor of\n                    <jats:styled-content style=\"fixed-case\">AGEs<\/jats:styled-content>\n                    . Muscle fibre atrophy and immunoreactivity for\n                    <jats:styled-content style=\"fixed-case\">AGEs<\/jats:styled-content>\n                    , Atrogin\u20101 (a muscle atrophy marker) and phosphorylated\n                    <jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content>\n                    \u2010activated protein kinase (\n                    <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content>\n                    ) expressions were markedly increased in human skeletal muscles from patients with diabetes as compared with control subjects. Moreover, in diabetic mice we found increased blood\n                    <jats:styled-content style=\"fixed-case\">AGEs<\/jats:styled-content>\n                    , less muscle mass, lower muscular endurance, atrophic muscle size and poor regenerative capacity, and increased levels of muscle\n                    <jats:styled-content style=\"fixed-case\">AGE<\/jats:styled-content>\n                    and receptor for\n                    <jats:styled-content style=\"fixed-case\">AGE<\/jats:styled-content>\n                    (\n                    <jats:styled-content style=\"fixed-case\">RAGE<\/jats:styled-content>\n                    ), Atrogin\u20101 and phosphorylated\n                    <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content>\n                    , which could be significantly ameliorated by Ala\u2010Cl. Furthermore,\n                    <jats:italic>in vitro<\/jats:italic>\n                    ,\n                    <jats:styled-content style=\"fixed-case\">AGEs<\/jats:styled-content>\n                    (in a dose\u2010dependent manner) reduced myotube diameters (myotube atrophy) and induced Atrogin\u20101 protein expression in myotubes differentiated from both mouse myoblasts and primary human skeletal muscle\u2010derived progenitor cells.\n                    <jats:styled-content style=\"fixed-case\">AGEs<\/jats:styled-content>\n                    exerted a negative regulation of myogenesis of mouse and human myoblasts. Ala\u2010Cl significantly inhibited the effects of\n                    <jats:styled-content style=\"fixed-case\">AGEs<\/jats:styled-content>\n                    on myotube atrophy and myogenesis. We further demonstrated that\n                    <jats:styled-content style=\"fixed-case\">AGEs<\/jats:styled-content>\n                    induced muscle atrophy\/myogenesis impairment via a\n                    <jats:styled-content style=\"fixed-case\">RAGE<\/jats:styled-content>\n                    \u2010mediated\n                    <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content>\n                    \u2010down\u2010regulation of the Akt signalling pathway. Our findings support that\n                    <jats:styled-content style=\"fixed-case\">AGEs<\/jats:styled-content>\n                    play an important role in diabetic myopathy, and that an inhibitor of\n                    <jats:styled-content style=\"fixed-case\">AGEs<\/jats:styled-content>\n                    may offer a therapeutic strategy for managing the dysfunction of muscle due to diabetes or ageing. Copyright \u00a9 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.4674","type":"journal-article","created":{"date-parts":[[2015,11,20]],"date-time":"2015-11-20T01:02:44Z","timestamp":1447981364000},"page":"470-482","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":154,"title":["Advanced glycation end\u2010products induce skeletal muscle atrophy and dysfunction in diabetic mice via a\n                    <scp>RAGE<\/scp>\n                    \u2010mediated,\n                    <scp>AMPK<\/scp>\n                    \u2010down\u2010regulated, Akt pathway"],"prefix":"10.1002","volume":"238","author":[{"given":"Chen\u2010Yuan","family":"Chiu","sequence":"first","affiliation":[{"name":"Institute of Toxicology, College of Medicine National Taiwan University  Taipei 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