{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:10:22Z","timestamp":1773011422858,"version":"3.50.1"},"reference-count":56,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      There is evidence demonstrating the risk of developing diabetes mellitus because of SARS\u2010CoV\u20102 infection. Therefore, further research is needed to determine pathological mechanisms at which SARS\u2010CoV\u20102 induces diabetes mellitus. This study therefore aims to understand the effect of SARS\u2010CoV\u20102 Main protease (M\n                      <jats:sup>pro<\/jats:sup>\n                      ) on glucose uptake and GLUT\u20104 translocation as well as AKT, GLUT\u20104, and IL\u20106 expression in skeletal muscle (C2C12).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, C2C12 cell preparations were exposed to different concentrations of M\n                      <jats:sup>pro<\/jats:sup>\n                      (2.5, 5, 10, 20, 40, 80, and 160\u2009nmol\/mL) for 24\u2009h to evaluate cytotoxicity and glucose uptake. For further assays, only the higher concentrations (40, 80, and 160\u2009nmol\/mL) were used. The impact of M\n                      <jats:sup>pro<\/jats:sup>\n                      on cell viability, glucose uptake, AKT, GLUT\u20104 and IL\u20106 expression, GLUT\u20104 translocation as well as lipid peroxidation were analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Following 24\u2009h of treatment with SARS\u2010CoV\u20102 M\n                      <jats:sup>pro<\/jats:sup>\n                      , C2C12 cells were viable. The baseline and insulin\u2010stimulated glucose uptake were impaired in the C2C12 cell line. M\n                      <jats:sup>pro<\/jats:sup>\n                      also compromised GLUT4 translocation and expression in the C2C12 cell line compared to the control. Baseline and Insulin\u2010stimulated AKT were not significantly altered in the presence of M\n                      <jats:sup>pro<\/jats:sup>\n                      . Intracellular and extracellular IL\u20106 levels were also affected by M\n                      <jats:sup>pro<\/jats:sup>\n                      . An increase in MDA levels, a marker for lipid peroxidation, was observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The observations suggest that the SARS\u2010CoV\u20102 M\n                      <jats:sup>pro<\/jats:sup>\n                      may be inducing an insulin\u2010resistant state and dysregulation of glucose metabolism. Further studies are warranted to fully elucidate the mechanisms underlying the development of new\u2010onset diabetes mellitus in patients with a history of COVID\u201019.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70383","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:05:45Z","timestamp":1772985945000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Main Protease From SARS\u2010CoV\u20102 Dysregulates Glucose Handling in the C2C12 Cell Line In Vitro: A Mechanistic Study"],"prefix":"10.1002","volume":"14","author":[{"given":"Praise Tatenda","family":"Nhau","sequence":"first","affiliation":[{"name":"Pharmacology Division, Faculty of Pharmacy Rhodes University Makhanda South 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