Idioma:

COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis

Barreto, Ester A ; Cruz, Amanda S ; Veras, Flavio P ; Martins, Ronaldo ; Bernardelli, Rafaella S ; Paiva, Isadora M ; Lima, Thais M ; Singh, Youvika ; Guimarães, Raphael C ; Damasceno, Samara ; Pereira, Nayara ; Alves, João Manoel ; Gonçalves, Tiago T ; Forato, Julia ; Muraro, Stéfanie P ; Souza, Gabriela F ; Batah, Sabrina Setembre ; Proenca-Modena, José L ; Mori, Marcelo A ; Cunha, Fernando Q ; Louzada-Junior, Paulo ; Cunha, Thiago M ; Nakaya, Helder I ; Fabro, Alexandre ; de Oliveira, Renê D R ; Arruda, Eurico ; Réa, Rosângela ; Réa Neto, Álvaro ; Fernandes da Silva, Miguel M ; Leiria, Luiz Osório

Proceedings of the National Academy of Sciences - PNAS, 2023-05, Vol.120 (21), p.e2217119120-e2217119120 [Periódico revisado por pares]

United States: National Academy of Sciences

Texto completo disponível

Citações Citado por

Enviar para

Título:
COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis
Autor: Barreto, Ester A ; Cruz, Amanda S ; Veras, Flavio P ; Martins, Ronaldo ; Bernardelli, Rafaella S ; Paiva, Isadora M ; Lima, Thais M ; Singh, Youvika ; Guimarães, Raphael C ; Damasceno, Samara ; Pereira, Nayara ; Alves, João Manoel ; Gonçalves, Tiago T ; Forato, Julia ; Muraro, Stéfanie P ; Souza, Gabriela F ; Batah, Sabrina Setembre ; Proenca-Modena, José L ; Mori, Marcelo A ; Cunha, Fernando Q ; Louzada-Junior, Paulo ; Cunha, Thiago M ; Nakaya, Helder I ; Fabro, Alexandre ; de Oliveira, Renê D R ; Arruda, Eurico ; Réa, Rosângela ; Réa Neto, Álvaro ; Fernandes da Silva, Miguel M ; Leiria, Luiz Osório
Assuntos: ACE2 ; Angiotensin-converting enzyme 2 ; Beta cells ; Biological Sciences ; Biopsy ; Blood ; Blood Glucose ; Coronaviruses ; COVID-19 ; COVID-19 - complications ; Diabetes mellitus ; Gluconeogenesis ; Glucose ; Hepatocytes ; Hormones ; Humans ; Hyperglycemia ; Hyperglycemia - complications ; Infections ; Liver ; Patients ; Retrospective Studies ; SARS-CoV-2 ; Severe acute respiratory syndrome coronavirus 2 ; Subgroups ; Viral diseases ; Viruses
É parte de: Proceedings of the National Academy of Sciences - PNAS, 2023-05, Vol.120 (21), p.e2217119120-e2217119120
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Edited by David E. Cohen, Brigham and Women’s Hospital, Boston, MA; received October 7, 2022; accepted April 19, 2023 by Editorial Board Member C. Ronald Kahn
Descrição: Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes hyperglycemia by infecting hepatocytes and increasing glucose production. We performed a retrospective cohort study including patients that were admitted at a hospital with suspicion of COVID-19. Clinical and laboratory data were collected from the chart records and daily blood glucose values were analyzed to test the hypothesis on whether COVID-19 was independently associated with hyperglycemia. Blood glucose was collected from a subgroup of nondiabetic patients to assess pancreatic hormones. liver biopsies were collected to assess the presence of SARS-CoV-2 and its transporters in hepatocytes. In human hepatocytes, we studied the mechanistic bases of SARS-CoV-2 entrance and its gluconeogenic effect. SARS-CoV-2 infection was independently associated with hyperglycemia, regardless of diabetic history and beta cell function. We detected replicating viruses in human hepatocytes from liver biopsies and in primary hepatocytes. We found that SARS-CoV-2 variants infected human hepatocytes in vitro with different susceptibility. SARS-CoV-2 infection in hepatocytes yields the release of new infectious viral particles, though not causing cell damage. We showed that infected hepatocytes increase glucose production and this is associated with induction of PEPCK activity. Furthermore, our results demonstrate that SARS-CoV-2 entry in hepatocytes occurs partially through ACE2- and GRP78-dependent mechanisms. SARS-CoV-2 infects and replicates in hepatocytes and exerts a PEPCK-dependent gluconeogenic effect in these cells that potentially is a key cause of hyperglycemia in infected patients.
Editor: United States: National Academy of Sciences
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis

United States: National Academy of Sciences

Buscando em bases de dados remotas. Favor aguardar.