The common diabetes drug could mediate hyperglycemia, which is caused when SARS-CoV-2 infects hepatocytes.
New study findings report that SARS-CoV-2 can infect hepatocytes, which are liver cells and can stimulate glucose production. The research was led by the University of São Paulo (USP) in Brazil and shows that this can lead to hyperglycemia, which is an illness like diabetes in patients who are hospitalized, regardless of a normal blood sugar level before being admitted.
“Hyperglycemia is a prevalent complication in hospitalized COVID-19 patients that occurs regardless of their diabetes history and is associated with a worse clinical outcome,” said the authors in a news release.
The study confirmed that diabetes presented a risk factor for patients with COVID-19 and could result in a death rate 3.5 times higher for individuals with type 1 diabetes, and twice as high for type 2 diabetes.
The authors also added that they were unaware if SARS-CoV-2 triggers hyperglycemia directly, but based their research on how the virus infects hepatocytes and increases the production of glucose to cause hyperglycemia.
“Viral entry into liver cells is partially mediated by cooperation between the proteins GRP78 and ACE2. The latter, known to permit cell invasion by the virus throughout the body, is present on the surface of human liver cells in a low molecular weight isoform instead of the regular one. This is one of the researchers’ novel findings. Previous studies suggested liver cells did not express ACE2,” said the authors in the press release.
The Center for Research on Inflammatory Diseases and the Research Innovation and Dissemination Center conducted a study with 269 individuals treated in the intensive care unit of Hospital das Clínicas and 663 individuals admitted with possible COVID-19.
“We succeeded in obtaining an almost perfect control group, with similar symptoms, negative PCR results, and the same hospital environment,” said Luiz Osório Silveira Leiria, a professor in the Department of Pharmacy at USP Ribeirão Preto Medical School.
The study found that the results of the human primary hepatocytes showed that the cells were infected with SARS-CoV-2 and in both cases the virus was found in the hepatocytes. However, the virus did not kill the hepatocytes, but was able to replicate and increase the glucose that was being produced.
According to the news release, the researchers used these results to test compounds that would be able to inhibit GRP78 and ACE2. The researchers found that metformin could aid treatment, as it is a drug for high blood sugar levels in type 2 diabetes.
“Other studies found that intensive therapy with insulin in the hospital doesn’t necessarily help these patients. A drug like metformin is more effective than insulin. Of course, metformin acts in various ways, but it’s a potential route to provide additional protection for these patients,” said Leiria.
The findings suggest metformin could assist individuals who were infected with SARS-CoV-2 when hyperglycemia is present.
SARS-CoV-2 infects liver, stimulating glucose production and contributing to severe form of COVID-19. EurekAlert!. News release. July 19, 2023. Accessed July 27, 2023. https://www.eurekalert.org/news-releases/996151.