Clinical studies have found impaired glucose homeostasis & ketoacidosis in COVID-19 patients - begs the question: does COVID-19/SARS-CoV-2 cause diabetes? We get closer to finding an answer with our new study out now in @NatMetabolism.
https://www.nature.com/articles/s42255-021-00347-1
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https://www.nature.com/articles/s42255-021-00347-1
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First, we checked if SARS-CoV-2 entry factors ACE2 and TMPRSS2 are expressed in pancreatic islets. They are, and seem to be specifically enriched in β cells compared to other populations.
We then infected purified pancreatic islets (excess donor material for transplantations) with SARS-CoV-2 and observed replication & release of new infectious virus particles. Co-detection of viral N protein and lineage marker PDX1 suggests endocrine cells are indeed infected.
With electron microscopy, we found viral particles in cells containing endocrine secretory vesicles. The number of these vesicles was reduced after infection. In the same cells, glucose-stimulated insulin secretion was impaired after infection (although effects are variable).
We then looked at patients deceased from COVID-19. In 4/4 patients, we found SARS-CoV-2 N protein in the pancreas. One patient had a rapid disease course, 3/4 had a slower course - lung already negative for viral proteins again, but still detectable in kidney (and pancreas).
For infected islets & patients, we checked which cell types are infected. We could detect little co-staining with primary β cell markers (insulin/C-pep), but with upstream lineage markers PDX1/NKX6.1 - infection may lead to hormone loss, but infected cells appear to be β cells.
Summary: #SARSCoV2 replicates in pancreatic islets, pancreas infected in patients w/ severe #COVID19. Infected cells likely β, infection
hormone loss, impaired insulin secretion. More data needed to answer whether COVID-19 may cause permanent diabetes https://www.nature.com/articles/s42255-021-00347-1

Amazing work done together with @janis_mue11er @Caco55762021 @KlegerLab @CRC1279 @SparrerLab @bcellorg @LickertHeiko and more 

