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Pathological Glucose Levels Enhance Entry Factor Expression and Hepatic SARS-CoV-2 Infection
Guocheng Rao1, Xiongbo Sang1, Xinyue Zhu1
1Department 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.
Journal of Cellular and Molecular Medicine
|May 30, 2025
Summary
High blood sugar (hyperglycaemia) significantly increases SARS-CoV-2 entry factors in liver cells, promoting viral infection. Glucose-lowering drugs may offer therapeutic benefits for COVID-19 patients with hyperglycemia.
Area of Science:
- Metabolic disorders and infectious diseases
- Virology and molecular biology
Background:
- Severe COVID-19 is linked to metabolic complications like hyperglycemia.
- The role of metabolic factors in SARS-CoV-2 infection and entry is not fully understood.
Purpose of the Study:
- To investigate the impact of hyperglycemia on SARS-CoV-2 entry factors and infection in liver cells.
- To explore the therapeutic potential of glucose-lowering drugs in this context.
Main Methods:
- Assessed SARS-CoV-2 entry factor expression (Ace2, Tmprss2, etc.) in liver cells under varying glucose conditions.
- Utilized pseudovirus cell systems to evaluate SARS-CoV-2 entry into hepatocytes.
- Tested the effects of glucose-lowering drugs (metformin, dapagliflozin, sitagliptin, exenatide) on viral entry and factor expression.
- Examined entry factor levels in liver samples from patients with nonalcoholic fatty liver disease and diabetes.
Main Results:
- Hyperglycemia, not hyperinsulinaemia or hyperlipidaemia, significantly upregulated SARS-CoV-2 entry factors in liver cells.
- mTOR inhibition attenuated the induction of entry factors by hyperglycemia.
- Pathological glucose levels enhanced SARS-CoV-2 entry into cultured hepatocytes.
- Glucose-lowering drugs reduced entry factor expression and viral infection in hepatocytes under hyperglycemic conditions.
- Elevated SARS-CoV-2 entry factors were observed in the livers of patients with NAFLD and diabetes.
Conclusions:
- Hyperglycemia is a critical susceptibility factor for hepatic SARS-CoV-2 infection.
- Glucose-lowering therapies show promise for treating COVID-19 in patients with comorbid hyperglycemia.
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