Some Covid-19 patients develop diabetes in the course of their infection. An international study with participation by the University of Basel has mapped how coronavirus attacks and destroys insulin-producing pancreatic cells. The researchers also identified a way to protect these cells.
Diabetes is considered a risk factor in contracting a severe bout of coronavirus SARS-CoV-2. That a severe Covid-19 infection can, conversely, lead to diabetes is less well known. Yet a number of studies have shown that roughly 15% of hospitalized Covid-19 patients are newly diagnosed with diabetes.
An international research team led by the Stanford University School of Medicine, including participation by researchers from the University of Basel and the University Hospital of Basel, has now been able to show that coronavirus can actually infect pancreatic beta cells. The scientists report their findings in the journal Cell Metabolism. Beta cells produce the hormone insulin, which stimulates tissue cells to absorb sugar from the blood, thus lowering blood sugar.
Alternative entry point
Unlike lung tissue, where coronavirus primarily uses a protein called ACE2 as a portal of entry into the cells, the beta cells of the pancreas have only low quantities of ACE2. For this reason, it has been unclear until now whether and how the virus enters these cells. To answer this question, the researchers analyzed tissue samples from seven deceased Covid-19 ‑patients in Basel.
The analysis found evidence of SARS-CoV-2 in the pancreatic beta cells of the victims. These cells also contained large quantities of a protein that the virus uses as an alternative entry point to ACE2: neuropilin-1 (NRP1). Laboratory tests on cultured beta cells further showed that infected cells produced less insulin and exhibited signs of die-off. When the researchers used an inhibitor to block neuropilin-1, the virus was much less successful at penetrating the cells.
The fact that infection of beta cells could be reduced in this way, at least in lab tests, shows that it might also be possible to protect these cells in patients with a severe case of Covid-19.
“Current research cannot say for sure whether sugar metabolism normalizes again in all Covid-19 patients after an infection, or whether and how often permanent diabetes may develop,” explains pathologist Dr. Matthias Matter of the University of Basel and the University Hospital Basel. Dr. Matter lead the parts of the study that were conducted in Basel. He says there is evidence that patients with “long Covid” – i.e. symptoms that persist after the infection has cleared – have signs of diabetes several weeks to months afterwards. It would therefore be extremely useful to develop a way to prevent lasting damage to the pancreas.
Featured image: Fluorescent microscopic image of cells: When SARS-CoV-2 (red) infects beta cells, they produce less insulin (green) and show signs of death. The cell nuclei are stained blue. (Fluorescent microscopic image: Chien-Ting Wu et al., Cell Metabolism)
Original publication: Chien-Ting Wu, Peter V. Lidsky, Yinghong Xiao, Ivan T. Lee, Ran Cheng, Tsuguhisa Nakayama, Sizun Jiang, Janos Demeter, Romina J. Bevacqua, Charles A. Chang, Robert L. Whitener, Anna K. Stalder, Bokai Zhu, Han Chen, Yury Goltsev, Alexandar Tzankov, Jayakar V. Nayak, Garry P. Nolan, Matthias S. Matter, Raul Andino, Peter K. Jackson, SARS-CoV-2 infects human pancreatic Î² cells and elicits Î² cell impairment, Cell Metabolism, 2021, , ISSN 1550-4131, https://doi.org/10.1016/j.cmet.2021.05.013. (https://www.sciencedirect.com/science/article/pii/S1550413121002308)
Provided by University of Basel