{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:07:07Z","timestamp":1791994027106,"version":"4.4.0"},"reference-count":74,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T00:00:00Z","timestamp":1556064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1D1A1B03036210"],"award-info":[{"award-number":["2017R1D1A1B03036210"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Skeletal muscle atrophy is defined as a reduction of muscle mass caused by excessive protein degradation. However, the development of therapeutic interventions is still in an early stage. Although glucagon\u2010like peptide\u20101 receptor (GLP\u20101R) agonists, such as exendin\u20104 (Ex\u20104) and dulaglutide, are widely used for the treatment of diabetes, their effects on muscle pathology are unknown. In this study, we investigated the therapeutic potential of GLP\u20101R agonist for muscle wasting and the mechanisms involved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Mouse C2C12 myotubes were used to evaluate the\n                      <jats:italic>in vitro<\/jats:italic>\n                      effects of Ex\u20104 in the presence or absence of dexamethasone (Dex) on the regulation of the expression of muscle atrophic factors and the underlying mechanisms using various pharmacological inhibitors. In addition, we investigated the\n                      <jats:italic>in vivo<\/jats:italic>\n                      therapeutic effect of Ex\u20104 in a Dex\u2010induced mouse muscle atrophy model (20 mg\/kg\/day i.p.) followed by injection of Ex\u20104 (100 ng\/day i.p.) for 12 days and chronic kidney disease (CKD)\u2010induced muscle atrophy model. Furthermore, we evaluated the effect of a long\u2010acting GLP\u20101R agonist by treatment of dulaglutide (1 mg\/kg\/week s.c.) for 3 weeks, in DBA\/2J\u2010mdx mice, a Duchenne muscular dystrophy model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ex\u20104 suppressed the expression of myostatin (MSTN) and muscle atrophic factors such as F\u2010box only protein 32 (atrogin\u20101) and muscle RING\u2010finger protein\u20101 (MuRF\u20101) in Dex\u2010treated C2C12 myotubes. The suppression effect was via protein kinase A and protein kinase B signalling pathways through GLP\u20101R. In addition, Ex\u20104 treatment inhibited glucocorticoid receptor (GR) translocation by up\u2010regulating the proteins of GR inhibitory complexes. In a Dex\u2010induced muscle atrophy model, Ex\u20104 ameliorated muscle atrophy by suppressing muscle atrophic factors and enhancing myogenic factors (MyoG and MyoD), leading to increased muscle mass and function. In the CKD muscle atrophy model, Ex\u20104 also increased muscle mass, myofiber size, and muscle function. In addition, treatment with a long\u2010acting GLP\u20101R agonist, dulaglutide, recovered muscle mass and function in DBA\/2J\u2010mdx mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>GLP\u20101R agonists ameliorate muscle wasting by suppressing MSTN and muscle atrophic factors and enhancing myogenic factors through GLP\u20101R\u2010mediated signalling pathways. These novel findings suggest that activating GLP\u20101R signalling may be useful for the treatment of atrophy\u2010related muscular diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12434","type":"journal-article","created":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T22:04:56Z","timestamp":1556143496000},"page":"903-918","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":181,"title":["Amelioration of muscle wasting by glucagon\u2010like peptide\u20101 receptor agonist in muscle atrophy"],"prefix":"10.1002","volume":"10","author":[{"given":"Yeonhee","family":"Hong","sequence":"first","affiliation":[{"name":"College of Pharmacy and Gachon Institute of Pharmaceutical Science Gachon University  Yeonsu\u2010ku Incheon Korea"},{"name":"Lee Gil Ya Cancer and Diabetes Institute Gachon University  Incheon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Han","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Gachon Institute of Pharmaceutical Science Gachon University  Yeonsu\u2010ku Incheon Korea"},{"name":"Lee Gil Ya Cancer and Diabetes Institute Gachon University  Incheon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang Won","family":"Jeong","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Gachon Institute of Pharmaceutical Science Gachon University  Yeonsu\u2010ku Incheon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheol Soo","family":"Choi","sequence":"additional","affiliation":[{"name":"Lee Gil Ya Cancer and Diabetes Institute Gachon University  Incheon Korea"},{"name":"Gachon Medical Research Institute Gil Hospital  Incheon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee\u2010Sook","family":"Jun","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Gachon Institute of Pharmaceutical Science Gachon University  Yeonsu\u2010ku Incheon Korea"},{"name":"Lee Gil Ya Cancer and Diabetes Institute Gachon University  Incheon Korea"},{"name":"Gachon Medical Research Institute Gil Hospital  Incheon 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