BREAKING NEWS! Brazilian Study Shockingly Finds That SARS-CoV-2 Directly Infects Liver Cells Or Hepatocytes To Cause Hyperglycemia!
SARS-CoV-2 is capable of infecting hepatocytes using GRP78 and ACE2 receptors and stimulate these cells to produce glucose through gluconeogenesis
: The COVID-19 pandemic has been an unprecedented global health crisis, affecting millions of lives worldwide. One of the concerning complications associated with this viral infection is hyperglycemia, a condition characterized by high blood glucose levels.
Researchers from the University of São Paulo in Brazil have now made a groundbreaking discovery, shedding light on the direct link between SARS-CoV-2, the virus responsible for COVID-19, and liver cells, or hepatocytes, resulting in hyperglycemia.
Hyperglycemia has been observed in hospitalized COVID-19 patients, even in those without a history of diabetes as covered in various past COVID-19 News
This phenomenon has been associated with worse clinical outcomes, making it crucial to understand its underlying causes. The study team sought to investigate whether SARS-CoV-2 infection directly triggers hyperglycemia by infecting hepatocytes and promoting glucose production through gluconeogenesis.
The stud team team conducted a retrospective cohort study, analyzing data from patients admitted to hospitals with suspected COVID-19. They collected clinical and laboratory information, including daily blood glucose values, to determine whether COVID-19 was independently linked to hyperglycemia. Additionally, the scientists collected blood samples from a subset of non-diabetic patients to assess pancreatic hormone levels. Postmortem liver biopsies were also examined to investigate the presence of SARS-CoV-2 and its transporters in hepatocytes.
The results of the study revealed a significant association between COVID-19 infection and hyperglycemia, irrespective of pre-existing diabetes or beta cell function.
Moreover, the study team detected replicating SARS-CoV-2 viruses in human hepatocytes from postmortem liver biopsies, as well as in primary hepatocytes in the laboratory.
Interestingly, different variants of SARS-CoV-2 displayed varying levels of infectivity in hepatocyt
es, with the omicron variant being less pathogenic but still capable of stimulating gluconeogenesis.
Further investigation into the mechanism of infection in hepatocytes unveiled that SARS-CoV-2 enters these liver cells through a cooperative process involving two key receptors, GRP78 and ACE2. Inhibition of both receptors reduced the virus's entry into hepatocytes, suggesting their joint role in the infection process.
Additionally, the study team discovered that infected hepatocytes increase glucose production, a finding associated with the stimulation of PEPCK activity, a critical enzyme in gluconeogenesis.
These findings have significant implications for COVID-19 patients and their clinical management. The study highlights the importance of controlling hepatic glucose production in hospitalized patients to improve clinical outcomes.
Understanding the direct link between SARS-CoV-2 and hyperglycemia may pave the way for new therapeutic approaches. For instance, drugs like metformin, used in type 2 diabetes treatment for inhibiting hepatic glucose production, could potentially offer protection against hyperglycemia in COVID-19 patients.
It must be stressed that hyperglycemia is a common feature in COVID-19 patients, regardless of their diabetic status, and its association with worse outcomes has been evident.
Although hyperglycemia can be caused when the immune system attacks the pancreatic cells that generate insulin, as in type 1 diabetes, it was noted in the study that the COVID-19 patients had no signs of pancreatic damage or disruptions in insulin production.
This was the key finding that inspired the study team to turn to the liver to see if there were problems there causing the hyperlycemia.
Senior author, Dr Luiz Osório Silveira Leiria, a professor at the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP) told Thailand Medical News, "Confirming the presence of receptors GRP78 and ACE2 in the liver cells was the cherry topping on the cake for our study, but the most significant result was that SARS-CoV-2 causes hyperglycemia directly, regardless of corticoid use, stress due to hospitalization, body weight and diabetes. It's the first time the virus has been shown to cause hyperglycemia directly.”
This new study findings from Brazil marks the first time that SARS-CoV-2 has been directly implicated as a cause of hyperglycemia. The study emphasizes the need for further research into the intricate relationship between the virus, liver cells, and glucose metabolism to better understand and treat this devastating pandemic.
The study findings were published in the peer reviewed journal: Proceedings of the National Academy of Sciences (PNAS).
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