Japanese researchers have identified a pivotal gene that mediates the effects of SARS-CoV-2 infection on blood sugar metabolism.

COVID-19 is best known for causing respiratory disease, but can also damage other organ systems; notably, disruption of blood sugar regulation can lead to new-onset diabetes. However, it is unclear how infection with the SARS-CoV-2 virus results in these effects.

In a study published in June in Metabolism, researchers from Osaka University reveal that COVID interferes with insulin signalling leading to diabetes.

"The insulin/IGF signalling pathway is a key pathway in the regulation of energy metabolism and cell survival," said Jihoon Shin, the first author of the study. "Therefore, we suspected that SARS-CoV-2 affects this signalling pathway to cause problems with blood sugar regulation."

To test this, the researchers analysed datasets of gene expression from patients, as well as in vivo and in vitro models, infected with SARS-CoV-2. They specifically looked for genes that were noticeably over-or under-expressed compared with uninfected patients, or cells.

"The results were striking," states Iichiro Shimomura, senior author from the varsity. "Infection with SARS-CoV-2 affected the expression of insulin/IGF signalling pathway components in the lung, liver, adipose tissue, and pancreatic cells. Moreover, these changes were attributed in part to activation of interferon regulatory factor 1 (IRF1)," Shimomura said.

Further investigation showed that IRF1 expression is elevated in older patients, men, obese individuals, and patients with diabetes. The synergistic effect of older age, male sex, obesity and diabetes with SARS-CoV-2 means that the expression of IRF1 occurs at an increased rate, which may explain why these patients are more vulnerable to COVID.

In addition, critical patients with COVID had higher IRF1 expression and lower insulin/IGF signalling pathway genes in their blood compared with noncritical patients. Finally, treating SARS-CoV-2-infected cells or an experimental model with hormonal factors such as dihydrotestosterone and dexamethasone that decreased IRF1 expression enhanced insulin/IGF signalling.

By identifying patients at greater risk of experiencing these effects and intervening to decrease IRF1 activation, some of the severe consequences of COVID-19 could be avoided in susceptible populations.