{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T19:58:16Z","timestamp":1780603096459,"version":"3.54.1"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T00:00:00Z","timestamp":1678060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>C\u2010peptide therapy exerts several positive actions on nerves, vasculature, smooth muscle relaxation, kidney function and bone. To date, the role of C\u2010peptide in preventing type 1 diabetes\u2010related muscle atrophy has not been investigated. Our aim was to evaluate if C\u2010peptide infusion prevents muscle wasting in diabetic rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty\u2010three male Wistar rats were randomly divided into three groups: normal control group, diabetic group and diabetic group plus C\u2010peptide. Diabetes was induced by streptozotocin injection, and C\u2010peptide was administered subcutaneously for 6\u00a0weeks. The blood samples were obtained at baseline, before streptozotocin injection and at the end of the study to assess C\u2010peptide, ubiquitin and other laboratory parameters. We also tested the ability of C\u2010peptide to regulate the skeletal muscle mass, the ubiquitin\u2013proteasome system, the autophagy pathway as well as to improve muscle quality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>C\u2010peptide administration reversed hyperglycaemia (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.02) and hypertriglyceridaemia (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.01) in diabetic plus C\u2010peptide rats compared with diabetic control rats. The diabetic\u2010control animals displayed a lower weight of the muscles in the lower limb considered individually than the control rats and the diabetic plus C\u2010peptide rats (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.03; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.03; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.04; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.004, respectively). The diabetic\u2010control rats presented a significantly higher serum concentration of ubiquitin compared with the diabetic plus C\u2010peptide and the control animals (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.02 and <jats:italic>P<\/jats:italic>\u00a0=\u00a00.01). In muscles of the lower limb, the pAmpk expression was higher in the diabetic plus C\u2010peptide than the diabetic\u2010control rats (in the gastrocnemius, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.002; in the tibialis anterior <jats:italic>P<\/jats:italic>\u00a0=\u00a00.005). The protein expression of Atrogin\u20101 in gastrocnemius and tibialis was lower in the diabetic plus C\u2010peptide than in diabetic\u2010control rats (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.02, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.03). After 42\u00a0days, the cross\u2010sectional area in the gastrocnemius of the diabetic plus C\u2010peptide group had been reduced by 6.6% while the diabetic\u2010control rats had a 39.5% reduction compared with the control animals (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.02). The cross\u2010sectional area of the tibialis and the extensor digitorum longus muscles was reduced, in the diabetic plus C\u2010peptide rats, by 10% and 11%, respectively, while the diabetic\u2010control group had a reduction of 65% and 45% compared with the control animals (both <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). Similar results were obtained for the minimum Feret's diameter and perimeter.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>C\u2010peptide administration in rats could protect skeletal muscle mass from atrophy induced by type 1 diabetes mellitus. Our findings could suggest that targeting the ubiquitin\u2013proteasome system, Ampk and muscle\u2010specific E3 ubiquitin ligases such as Atrogin\u20101 and Traf6 may be an effective strategy for molecular and clinical intervention in the muscle wasting pathological process in T1DM.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13210","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T03:44:49Z","timestamp":1678160689000},"page":"1117-1129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Preventing muscle wasting: pro\u2010insulin C\u2010peptide prevents loss in muscle mass in streptozotocin\u2010diabetic rats"],"prefix":"10.1002","volume":"14","author":[{"given":"Samantha","family":"Maurotti","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine University Magna Gr\u00e6cia  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Pujia","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Science University Magna Gr\u00e6cia  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Galluccio","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University Magna Gr\u00e6cia  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saverio","family":"Nucera","sequence":"additional","affiliation":[{"name":"Department of Health Science University Magna Gr\u00e6cia  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Musolino","sequence":"additional","affiliation":[{"name":"Department of Health Science University Magna Gr\u00e6cia  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Mare","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University Magna Gr\u00e6cia  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Frosina","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Science University Magna Gr\u00e6cia  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Rita","family":"Noto","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Science University Magna Gr\u00e6cia  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Mollace","sequence":"additional","affiliation":[{"name":"Department of Health Science University Magna Gr\u00e6cia  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Romeo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Science University Magna Gr\u00e6cia  Catanzaro Italy"},{"name":"Department of Molecular and Clinical Medicine University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Pujia","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Science University Magna Gr\u00e6cia  Catanzaro Italy"},{"name":"Research Center for the Prevention and Treatment of Metabolic Diseases (CR METDIS) University Magna Gr\u00e6cia  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Montalcini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University Magna Gr\u00e6cia  Catanzaro Italy"},{"name":"Research Center for the Prevention and Treatment of Metabolic Diseases (CR METDIS) University Magna Gr\u00e6cia  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000479"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5448.2010.00699.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2017.10.005"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-017-0979-9"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13061909"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9136(199601)13:1<40::AID-DIA991>3.0.CO;2-U"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-5491.2002.00702.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1017943200785"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)42448-4"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000169976.20029.64"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118968"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)42013-9"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.276.5.C1132"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/db18-0416"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.09.013"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00400-3"},{"key":"e_1_2_8_18_1","volume-title":"The next four decades. The older population in the United States: 2010 to 2050, population estimates and projections","author":"Vincent GK","year":"2010"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0881"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-017-1286-5"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-020-00716-0"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/62.7.765"},{"key":"e_1_2_8_23_1","first-page":"254","article-title":"Laboratory methodology for the histological study of skeletal muscle","volume":"35","author":"Leiva\u2010Cepas F","year":"2018","journal-title":"Archivos de Medicina del Deporte"},{"key":"e_1_2_8_24_1","first-page":"532","article-title":"A reagent for the single\u2010step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples","volume":"15","author":"Chomczynski P","year":"1993","journal-title":"Biotechniques"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110977"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.224972"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2012.06.019"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0039"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00330.2009"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12-0716"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.70057"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-016-0031-z"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201006098"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2011.04.018"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1113\/EP085049"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-004-1602-5"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.114.16.2903"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2015.3845"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.09.010"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90585-X"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12899"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13210","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.13210","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13210","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T04:17:45Z","timestamp":1692677865000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.13210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,6]]},"references-count":40,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1002\/jcsm.13210"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.13210","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,6]]},"assertion":[{"value":"2022-04-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}