COVID-19 has been linked to cases of new-onset diabetes, diabetes-related emergencies and a higher death rate among diabetes patients.While this suggests that SARS-CoV-2, the virus that causes COVID-19, may infect and damage the insulin-producing beta cells of the pancreas, that does not appear to be the case, according to a report by researchers at Vanderbilt University Medical Center published in the journal Cell Metabolism, according to a press release.
“This is important information in terms of understanding the interaction of diabetes and SARS-CoV-2 and COVID-19,” said Katie Coate, PhD, who led the study with Jeeyeon Cha, MD, PhD. “There are other potential pathways for how SARS-CoV-2 infects cells, and these are just beginning to be described or are as yet undiscovered.”
However, these findings do not completely exclude the possibility that COVID-19 may damage beta cells indirectly, the researchers cautioned.
Infection by SARS-CoV-2 appears to involve a two-step process. First, the “spike” protein that protrudes from the virus must attach to a receptor called ACE2 on the surface of certain cells in the lungs and elsewhere in the body.
Then a cellular protease, the best known of which is called TMPRSS2, must chop up the spike protein, enabling the virus to fuse into the cell membrane and “break into” the cell. Once inside, the virus hijacks the cell’s genetic machinery to make copies of its RNA.
To investigate the possibility that SARS-CoV-2 can directly target beta cells using these pathways, the VUMC team used a variety of techniques to examine isolated human islets and pancreatic tissue for co-factor gene expression and for the presence of ACE2 and TMPRSS2 proteins.
The researchers found that pancreatic islet beta cells do not co-express genes or proteins for two cellular co-factors essential for SARS-CoV-2 infection. This observation makes it unlikely that infection of the insulin-producing pancreatic beta cells leads to the development or worsening of diabetes.
An independent study from investigators at the University of Florida published in the same issue of Cell Metabolism reached a similar conclusion.
While the researchers did not find ACE2 or TMPRSS2 proteins in beta cells from donors with and without diabetes, the proteins were present in the microvasculature of the pancreas and in the ducts that connect the pancreas to the digestive system.
