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However, the potential role of these metabolic risk factors in SARS\u2010CoV\u20102 infection and entry factor expression remains unknown. Here we report the implication of hyperglycaemia in SARS\u2010CoV\u20102 infection and therapy. Hyperglycaemia, instead of hyperinsulinaemia and hyperlipidaemia, can significantly induce the expression of SARS\u2010CoV\u20102 entry factors (\n                    <jats:italic>Ace2<\/jats:italic>\n                    ,\n                    <jats:italic>Tmprss2<\/jats:italic>\n                    ,\n                    <jats:italic>Tmprss4<\/jats:italic>\n                    ,\n                    <jats:italic>Furin<\/jats:italic>\n                    and\n                    <jats:italic>Nrp1<\/jats:italic>\n                    ) in liver cells, but not in lung and pancreatic cells, which is attenuated by mTOR inhibition. Correspondingly, pathological glucose levels promote SARS\u2010CoV\u20102 entry into cultured hepatocytes in pseudovirus cell systems. Conversely, representative glucose\u2010lowering drugs (metformin, dapagliflozin, sitagliptin and exenatide) are able to diminish the enhancement of entry factor expression and SARS\u2010CoV\u20102 infection in cultured hepatocytes under pathological glucose conditions. Intriguingly, SARS\u2010CoV\u20102 entry factors are increased in the livers of nonalcoholic fatty liver disease and diabetes patients. These results define hyperglycaemia as a key susceptibility factor for hepatic SARS\u2010CoV\u20102 infection, and provide insights into the clinical application of glucose\u2010lowering therapies in COVID\u201019 patients under comorbid hyperglycaemia conditions.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.70581","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:54:18Z","timestamp":1748566458000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pathological Glucose Levels Enhance Entry Factor Expression and Hepatic\n                    <scp>SARS<\/scp>\n                    \u2010\n                    <scp>CoV<\/scp>\n                    \u20102 Infection"],"prefix":"10.1111","volume":"29","author":[{"given":"Guocheng","family":"Rao","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Department of Biotherapy, Center for Diabetes and Metabolism Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiongbo","family":"Sang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Department of Biotherapy, Center for Diabetes and Metabolism Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyue","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Department of Biotherapy, Center for Diabetes and Metabolism Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sailan","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Department of Biotherapy, Center for Diabetes and Metabolism Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Department of Biotherapy, Center for Diabetes and Metabolism Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Department of Endocrinology and Metabolism Gansu Provincial Hospital  Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Department of Biotherapy, Center for Diabetes and Metabolism Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9808-3892","authenticated-orcid":false,"given":"Xianghui","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Department of Biotherapy, Center for Diabetes and Metabolism Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital Sichuan University  Chengdu Sichuan 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