Insulin was discovered 100 years ago, a hormone produced by the human pancreas that plays a key role in maintaining correct blood glucose levels. When a person has diabetes, their glucose levels are altered. Not being controlled, it can be a risk factor for developing severe COVID-19if the person is infected with the coronavirus and that is why it is a priority today that they receive the full vaccination schedule as soon as possible. In Japan, they found a mechanism that contributes to people with diabetes suffering from these more severe conditions.
It was described by researchers from the University of Osaka in Japan: the coronavirus that causes COVID-19 disease binds to a cell surface protein whose expression is favored by high levels of insulin in the blood in older people, those with obesity and with diabetes.
Before the pandemic, it was known that keeping blood insulin levels within strict and healthy parameters should be a daily goal for people with diabetes. But now researchers in Japan have found that Regulating blood insulin levels can even help reduce the risk of COVID-19.
As reported in their study published this month in the specialized journal Diabetes, published by the American Diabetes Association, Japanese researchers discovered that a protein called GRP78 helps the virus that causes COVID-19 to bind to and enter cells.
GRP78 is a protein found in adipose tissue (that is, in fat). Older, obese, and diabetic people are more vulnerable to COVID-19 and, although the reasons for this are still not entirely clear, the Osaka University team shed light on this issue.
“It was recently suggested that adipose tissue could be an important reservoir for the SARS-CoV-2 coronavirus, the virus that causes COVID-19,” said lead study author Jihoon Shin. “For this reason, we wanted to investigate whether there is any relationship between excess adipose tissue in elderly, obese, and diabetic patients and their vulnerability to COVID-19.”
To that end, the researchers looked at GRP78, which has recently been suggested to be involved in the interaction of the coronavirus with human cells. The main route by which the virus enters human cells is through a spike protein on the viral surface that binds to a protein on the human cell surface called angiotensin converting enzyme 2 (ACE2).
Shin and his colleagues found that the Spiga protein can also bind directly to GRP78. They also found that the presence of GRP78 increases binding with ACE2. To get an idea of the implication of GRP78 in the vulnerability of COVID-19, they investigated the amount of GRP78 protein present in the tissues of elderly, obese, and diabetic patients.
“The results were very clear,” explained lead author Iichiro Shimomura. “The expression of the GRP78 gene was highly regulated in adipose tissue, and it was elevated with increasing age, obesity, and diabetes.”
Aging, obesity, and diabetes are known to be associated with increased levels of insulin in the blood. The group wondered if insulin was involved in the expression of GRP78. They found that exposing the cells to insulin induced the expression of the GRP78 protein. And what is more important, found that treatment with widely prescribed antidiabetic drugs that reduce insulin levels was able to reduce the level of GRP78 expression. They went one step further and showed that exercise and caloric restriction in a mouse model also worked to reduce GRP78 levels in adipose tissue.
“Our results suggest that an elevated level of insulin in the blood is an important risk factor that can predispose elderly, obese, and diabetic people to COVID-19 infection. Therefore, the control of insulin in the blood with pharmacological interventions or with interventions, such as physical activity, could help reduce the risk of these patients, ” said Shin.
Taking into account the health, social and economic impact that the pandemic has had in the world, the results of the Japanese study provide important information on how to reduce the risk of infection in these vulnerable patients ”. Reducing GRP78 expression through pharmacological or environmental interventions could improve outcomes in these patients.
Last May, another study by researchers from the University of Southeastern California in the United States that was published in the Journal of Biological Chemistry had also provided information on this protein related to the COVID-19 pandemic. They suggested how therapies targeting the GRP78 protein could offer additional protection against COVID-19 and other emerging coronaviruses in the future.
GRP78 is a type of molecule that helps regulate the correct folding of proteins, especially when a cell is under stress. But in some cases, viruses can hijack these chaperones to infect target cells, where they reproduce and spread. GRP78 has been implicated in the spread of other serious viruses, such as Ebola and Zika. They found that GRP78 serves as a co-receptor and stabilizing agent between ACE2 and SARS-CoV-2, improving recognition of the virus’s Spike protein and allowing more efficient entry of the virus into host cells.
That study provided the first experimental evidence in support of computer model predictions, demonstrating that GRP78 binds to the coronavirus Spike protein in cells. Furthermore, computer modeling showed that the coronavirus variants that are more infectious bind more to GRP78.