| Autor: |
Millette K; USC., Cuala J; USC., Wang P; USC., Marks C; USC., Woo V; USC., Hayun M; USC., Kang H; USC., Martin M; UCLA., Dhawan S; City of Hope., Chao L; CHLA., Fraser S; USC., Junge J; University of Southern California., Lewis M; Bioqual., Georgia S; Children's Hospital Los Angeles. |
| Jazyk: |
angličtina |
| Zdroj: |
Research square [Res Sq] 2021 Jul 20. Date of Electronic Publication: 2021 Jul 20. |
| DOI: |
10.21203/rs.3.rs-592374/v1 |
| Abstrakt: |
Increasing evidence of new-onset diabetes during the COVID19 pandemic indicates that the SARS-CoV2 virus may drive beta-cell dysfunction leading to diabetes, but it is unclear if it is a primary or secondary effect. Here, we present evidence of SARS-CoV-2 infection of pancreatic beta cells in vivo using a robust and reproducible non-human primates model of mild to moderate COVID19 pathogenesis. Pancreas from SARS-CoV-2 infected subjects were positive for the SARS-CoV2 spike protein by immunohistochemistry and structures indicative of viral replication were evident by electron microscopy. Total beta cell area was decreased in SARS-CoV-2-infected pancreas, attributable to beta cell atrophy. Beta cell granularity was decreased. These histologic phenotypes persisted beyond the duration of the clinical disease course. Detailed electron microscopy of SARS-CoV-2 infected beta-cells revealed ultrastructural hallmarks of beta cell stress that are seen in islets of patients with Type 2 diabetes, including disrupted mitochondria and dilated endoplasmic reticulum. To assess the metabolic status of beta cells from SARS-CoV-2-infected subjects, we used fluorescence life-time imaging to measure the ratio of free and bound NADH as a surrogate of glycolytic and oxidative metabolism. We report an increase in free NADH levels, suggesting that beta cells from SARS-CoV-2-infected subjects adopt a more glycolytic metabolic profile. Taken together, we conclude that SARS-CoV-2 infection induces beta cell stress that may compromise beta-cell function beyond the duration of the disease course. This raises the possibility that the beta cell stress and injury may have clinical implications of the long-term future health of patients that have recovered from COVID19. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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