TY - JOUR

T1 - Beta-cells from patients with COVID-19 and from isolated human islets exhibit ACE2, DPP4, and TMPRSS2 expression, viral infiltration and necroptotic cell death

AU - Steenblock, Charlotte

AU - Richter, Stefanie

AU - Berger, Ilona

AU - Barovic, Marko

AU - Schmid, Janine

AU - Schubert, Undine

AU - Jarzebska, Natalia

AU - von Massenhausen, Anne

AU - Linkermann, Andreas

AU - Schurmann, Annette

AU - Pablik, Jessica

AU - Evert, Katja

AU - Rodionov, Roman

AU - Semenova, Natalia

AU - Zinslering, Vsevolod

AU - Gainetdinov, Raul

AU - Baretton, Gustavo

AU - Lindemann, Dirk

AU - Solimena, Michaele

AU - Ludwig, Barbara

AU - Bornstein , Stefan

PY - 2020

Y1 - 2020

N2 - Here we report a possible mechanistic link between coronavirus disease 2019 (COVID-19) and diabetes. In addition to its known role on the respiratory system, the human coronavirus SARS-CoV-2 has been shown to affect the endocrine system including the pancreas 1-4. It has been suggested that the virus can induce type 1 diabetes 5-8. Therefore, we isolated human pancreatic islets and examined the expression of angiotensin-converting enzyme 2 (ACE2) and the protease TMPRSS2, known to be important for SARS-CoV-2 entry 9. Furthermore, we investigated the expression of an alternative entry receptor, dipeptidyl peptidase-4 (DPP4 also known as CD26) 10. We found all three proteins expressed in pancreatic beta-cells and confirmed that beta-cells are permissive to infection with SARS-CoV-2 pseudoviruses. Additionally, we performed a comprehensive analysis of ACE2, TMPRSS2 and DPP4 expression in pancreata of 10 patients who died of COVID-19. We report significant variation between the samples and detected the highest levels of ACE2 and DPP4 expression in patients exhibiting SARS-CoV-2 infiltration shown by confocal microscopy, RNAscope and electron microscopy. Furthermore, necroptotic cell death was observed in beta-cells of the COVID-19 patients. Taken together, these data suggest that SARS-CoV-2 viral infection of pancreatic beta-cells may trigger necroptosis and islet impairment.

AB - Here we report a possible mechanistic link between coronavirus disease 2019 (COVID-19) and diabetes. In addition to its known role on the respiratory system, the human coronavirus SARS-CoV-2 has been shown to affect the endocrine system including the pancreas 1-4. It has been suggested that the virus can induce type 1 diabetes 5-8. Therefore, we isolated human pancreatic islets and examined the expression of angiotensin-converting enzyme 2 (ACE2) and the protease TMPRSS2, known to be important for SARS-CoV-2 entry 9. Furthermore, we investigated the expression of an alternative entry receptor, dipeptidyl peptidase-4 (DPP4 also known as CD26) 10. We found all three proteins expressed in pancreatic beta-cells and confirmed that beta-cells are permissive to infection with SARS-CoV-2 pseudoviruses. Additionally, we performed a comprehensive analysis of ACE2, TMPRSS2 and DPP4 expression in pancreata of 10 patients who died of COVID-19. We report significant variation between the samples and detected the highest levels of ACE2 and DPP4 expression in patients exhibiting SARS-CoV-2 infiltration shown by confocal microscopy, RNAscope and electron microscopy. Furthermore, necroptotic cell death was observed in beta-cells of the COVID-19 patients. Taken together, these data suggest that SARS-CoV-2 viral infection of pancreatic beta-cells may trigger necroptosis and islet impairment.

KW - COVID-19

UR - https://www.researchsquare.com/article/rs-88524/v1

UR - https://europepmc.org/article/ppr/ppr224646

M3 - Review article

JO - Nature Metabolism

JF - Nature Metabolism

SN - 2522-5812

ER -