National Institutes of Health–sponsored research examines the underlying cause of COVID-19–induced diabetes.
Building on research first released in 2020 indicating COVID-19 caused diabetes in rare cases, 2 new National Institutes of Health–supported studies now illustrate just how the coronavirus can bring on the disease.
Specifically, the research shows how SARS-CoV-2, the virus that causes COVID-19, targets and impairs the body’s insulin-producing cells and alters islet function.
“Earlier lab studies had suggested that SARS-CoV-2 can infect human beta cells,” explained NIH Director Francis Collins, MD, PhD, in a blog post. Individuals develop type 1 diabetes (T1D) when beta cells in the pancreas fail to secrete enough insulin to allow the body to optimally metabolize food.
However, the new research indicates “the virus can replicate in these insulin-producing beta cells to make more copies of itself and spread to other cells,” Collins said. The 2 studies were published online May 18 and May 19 in Cell Metabolism.
Researchers in California and New York built on earlier work exploring this relationship and ultimately “confirmed infection of pancreatic beta cells in autopsy samples from people who died of COVID-19.”
Teams were led by Peter Jackson, PhD, of Stanford University School of Medicine, and Shuibing Chen, PhD, of Weill Cornell Medicine. Further studies conducted by Jackson’s team indicated the virus may preferentially infect insulin-producing beta cells and leads directly to the death of some beta cells. The team led by Chen also found signs of SARS-CoV-2 in insulin-producing beta cells, in addition to other pancreatic cell types.
“Beta cells and other cell types in the pancreas express the ACE2 receptor protein, the TMPRSS2 enzyme protein, and neuropilin 1 (NRP1), all of which SARS-CoV-2 depends upon to enter and infect human cells,” Collins wrote. Notably, blocking NRP1 can prevent beta cell death.
Both teams saw evidence that COVID-19 results in reduced production and release of insulin from pancreatic islet tissue and can induce transdifferentiation in the remaining beta cells, essentially reprogramming them.
“In this process, the cells begin producing less insulin and more glucagon, a hormone that encourages glycogen in the liver to be broken down into glucose. They also began producing higher levels of a digestive enzyme called trypsin 1,” Collins said. However, the teams again proved this process could be reversed.
Although the consequences of beta cell transdifferentiation are still unclear, researchers hypothesize it could worsen insulin deficiency and increase blood glucose levels in those affected.
“It would be of value to evaluate patient records to determine the time of onset of COVID-19-induced pneumonia, marking severe lung infection, compared with the evolution of hyperglycemia as a marker of pancreatic damage and a diabetes-like effect on insulin secretion,” wrote Jackson and colleagues.
Future research on how SARS-CoV-2 reaches the pancreas, in addition to understanding the role of the immune system in the resulting damage, is warranted.