In a recent study, researchers found that coronavirus can lead to metabolism problems, and sometimes even diabetes because it affects insulin signalling.
The novel coronavirus is transmitted by inhaling infected droplets in the air, which affects the lungs first.
But researchers have found that its harmful effects go beyond the lungs. In a groundbreaking study, a team in Japan say that they’ve singled out a critical gene that mediates the effects of SARS-CoV-2 infection on blood sugar mechanism.
Osaka University scientists published a study in the June issue of the journal Metabolism, stating that “Covid-19 can cause multiple organ damages as well as metabolic abnormalities such as hyperglycemia, insulin resistance, and new onset of diabetes” by interfering with insulin signalling.
The scientists note that their aim was to “investigate whether SARS-CoV-2 infection impairs the insulin/IGF signalling pathway in the host cell/tissue, and if so, the potential mechanism and association with COVID-19 pathology.”
They point out that “SARS-CoV-2 not only infects the respiratory [tract] but also other organs and cells, including liver, adipose tissue [body fat], and pancreas.”
“Multiple organ failure critically contributes to the severity and mortality of Covid-19, but the molecular mechanisms have not been fully explained,” they added.
“The insulin/IGF [insulin-like growth factor] signalling pathway is a key pathway in the regulation of energy metabolism and cell survival,” says Jihoon Shin, first author on the study. “Therefore, we suspected that SARS-CoV-2 affects this signalling pathway to cause problems with blood sugar regulation.”
To test their hypothesis that coronavirus affects the insulin signalling pathway, the researchers went through datasets of gene expression from patients, as well as in vivo (live animals) and in vitro (lab culture) models, infected with SARS-CoV-2. They especially sought genes that were noticeably over- or under-expressed compared with uninfected patients, animals or cells.
“The results were striking,” states Iichiro Shimomura, senior author of the study. “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).”
The authors explained that “The high expression of IRF1 in Covid-19 patients with older age, male sex, obesity, and diabetes may exacerbate the impairment of the insulin/IGF signaling pathway, which may potentially contribute to severe tissue damage and metabolic abnormalities, thereby leading to critical outcomes in Covid-19.”
“Higher basal IRF1 expression by pathological (older age, male sex, obesity, and diabetes) and/or genetic (IRF1 intron variant rs17622656-A) reasons in respiratory, metabolic, and/or endocrine organs might contribute to synergistic upregulation of IRF1 in response to SARS-CoV-2 infection, which may make the people more vulnerable to COVID-19,” the authors continued.
Because IRF1 is elevated in older patients, men, obese individuals, and patients with diabetes, it makes them more vulnerable to Covid-19 infection. Moreover, critical coronavirus patients had higher IRF1 expression and lower insulin/IGF signalling pathway genes in their blood compared with noncritical patients.
“In the present study, we showed that hormonal interventions … inhibited the gene expression of IRF1 and enhanced that of the insulin/IGF signalling pathway.”
“Our findings suggest that SARS-CoV-2 infection impairs insulin/IGF signalling by increasing IRF1 expression, thereby disrupting blood sugar metabolism. Decreasing IRF1 expression by treatment with factors such as dihydrotestosterone and dexamethasone could help mitigate the effects of COVID-19,” says Shin.
The authors hope that this study “will be helpful for better comprehension of Covid-19 pathology and for identifying therapeutic approaches.”
Covid-19 can negatively impact multiple organ systems. “Treatment strategies that could alleviate the effect of the disease on blood sugar metabolism could be vitally important,” a news release notes.
Some of the severe consequences of the coronavirus could be avoided in vulnerable patients with the identification of individuals from elevated risk groups and intervention to decrease IRF1 activation.