Evidence mapPaperPMID 40442985Full record

ArticleJournal of cellular and molecular medicine2025

Pathological Glucose Levels Enhance Entry Factor Expression and Hepatic SARS-CoV-2 Infection.

Guocheng Rao, Xiongbo Sang, Xinyue Zhu, Sailan Zou, Yanyan Zhang, Wei Cheng, Yan Tian, Xianghui Fu

Abstract read
In one paragraph

Article in Journal of cellular and molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Guocheng RaoDepartment 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.
Xiongbo SangDepartment 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.
Xinyue ZhuDepartment 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.
Sailan ZouDepartment 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.
Yanyan ZhangDepartment 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.
Wei ChengDivision of Pulmonary and Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Yan TianDepartment 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.
Xianghui FuDepartment 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.ORCID 0000-0001-9808-3892

Funding

1.3.5 Project for Disciplines Excellence, West China Hospital, Sichuan University ZYJD23005National Natural Science Foundation of China 81970561National Natural Science Foundation of China 82172986National Natural Science Foundation of China 92157205National Science and Technology Major Project 2023ZD0507500Postdoctoral Research Fund of West China Hospital, Sichuan University 2024HXBH184
6 · The paper itself

Abstract

Accumulating clinical evidence suggests an intricate relationship between severe COVID-19 and preexisting metabolic complications, which share some metabolic dysregulations, including hyperglycaemia, hyperinsulinaemia and hyperlipidaemia. However, the potential role of these metabolic risk factors in SARS-CoV-2 infection and entry factor expression remains unknown. Here we report the implication of hyperglycaemia in SARS-CoV-2 infection and therapy. Hyperglycaemia, instead of hyperinsulinaemia and hyperlipidaemia, can significantly induce the expression of SARS-CoV-2 entry factors (Ace2, Tmprss2, Tmprss4, Furin and Nrp1) in liver cells, but not in lung and pancreatic cells, which is attenuated by mTOR inhibition. Correspondingly, pathological glucose levels promote SARS-CoV-2 entry into cultured hepatocytes in pseudovirus cell systems. Conversely, representative glucose-lowering drugs (metformin, dapagliflozin, sitagliptin and exenatide) are able to diminish the enhancement of entry factor expression and SARS-CoV-2 infection in cultured hepatocytes under pathological glucose conditions. Intriguingly, SARS-CoV-2 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-CoV-2 infection, and provide insights into the clinical application of glucose-lowering therapies in COVID-19 patients under comorbid hyperglycaemia conditions.

Indexed as

COVID-19GlucoseHyperglycemiaLiverSARS-CoV-2Virus InternalizationAngiotensin-Converting Enzyme 2AnimalsFurinHepatocytesHumansHypoglycemic AgentsMaleNon-alcoholic Fatty Liver DiseaseSerine EndopeptidasesACE2 protein, humanAngiotensin-Converting Enzyme 2FurinGlucoseHypoglycemic AgentsSerine EndopeptidasesTMPRSS2 protein, humanCOVID‐19diabetesglucose‐lowering drugsmetabolic dysregulationNAFLD

Identifiers

PMID40442985
PMCPMC12122388

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.