Researchers at Case Western Reserve University and University Hospitals have identified an enzyme that blocks insulin produced in the body. This discovery could provide a new target for diabetes treatment.
Their study was published Dec. 5 in the journal cellfocuses on nitric oxide, a compound that dilates blood vessels, improves memory, fights infections, and stimulates the release of hormones, among other functions. How nitric oxide performs these activities has long been a mystery.
Researchers have discovered a novel “carrier” enzyme (called SNO-CoA-assisted nitrosylase, or SCAN) that binds nitric oxide to proteins such as receptors for insulin action.
They found that the SCAN enzyme is essential for normal insulin action, but also found that SCAN activity is increased in diabetic patients and diabetic mice. Mouse models lacking the SCAN enzyme appear to be protected from diabetes, suggesting that too much nitric oxide on proteins may be the cause of such diseases.
“We show that blocking this enzyme can prevent diabetes, but the impact extends to many diseases that are likely to be caused by the novel enzyme that adds nitric oxide,” said lead author of the study. said researcher Jonathan Stamler, Distinguished Professor of the Robert S. and Sylvia K. Reitman Family Foundation. He is Professor of Cardiovascular Innovation at Case Western Reserve School of Medicine and Director of the Harrington Discovery Institute at University Hospitals. “Blocking this enzyme could lead to new treatments.”
Given this discovery, the next step could be to develop drugs against this enzyme, he said.
The research team included Zhou Hualin and Richard Premont of Case Western Pre-Medical College and University Hospital, and students Zach Grimmett and Nicholas Benetos of the university’s Medical Scientist Training Program.
Many human diseases, including Alzheimer’s disease, cancer, heart failure, and diabetes, are thought to be caused or promoted by nitric oxide binding in excess to key proteins. Stamler said the discovery focuses attention on the enzyme that attaches nitric oxide.
When you have diabetes, your body often doesn’t respond properly to insulin. As a result, blood sugar levels rise and remain in the bloodstream, which can cause serious health problems over time. According to a report from the Centers for Disease Control, people with diabetes are more likely to suffer from conditions such as heart disease, vision loss, and kidney disease.
However, the reason why insulin stops working is not well understood.
Excess nitric oxide is thought to be involved in many diseases, but because the molecule is highly reactive and cannot be specifically targeted, its therapeutic potential is limited, Stamler said. said.
“This paper shows that dedicated enzymes mediate many of the effects of nitric oxide,” he said. “Here, we discovered an enzyme that controls insulin by adding nitric oxide to the insulin receptor. If the enzyme’s activity is too strong, it causes diabetes. However, many enzymes attach to many proteins. Because of the addition of nitric oxide, new treatments for many diseases have been proven.”
For more information, please contact Bill Lubinger at William.lubinger@case.edu.
This article was originally published on December 8, 2023.
