Researchers reveal previously unknown cause of diabetes

A groundbreaking study conducted by researchers from Case Western Reserve University and University Hospitals has uncovered a promising discovery in the fight against diabetes: the identification of an enzyme that obstructs insulin production in the body.

Published in the prestigious journal Cell, the research sheds light on the role of nitric oxide, a compound known for its diverse physiological functions including blood vessel dilation, memory enhancement, immune response facilitation, and hormonal regulation.

The research team pinpointed a previously unknown enzyme, termed SNO-CoA-assisted nitrosylase (SCAN), responsible for attaching nitric oxide to various proteins, including the insulin receptor.

They observed that SCAN enzyme activity was crucial for normal insulin function. Intriguingly, heightened levels of SCAN activity were detected in both diabetic patients and diabetic mice models.

Further investigations revealed that mice lacking the SCAN enzyme exhibited resistance to diabetes, suggesting a potential link between excessive nitric oxide on proteins and the development of diabetes.

Lead researcher Jonathan Stamler, the Robert S. and Sylvia K. Reitman Family Foundation Distinguished Professor of Cardiovascular Innovation at the Case Western Reserve School of Medicine and president of Harrington Discovery Institute at University Hospitals, emphasized the significance of the findings.

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“We show that blocking this enzyme protects from diabetes, but the implications extend to many diseases likely caused by novel enzymes that add nitric oxide. Blocking this enzyme may offer a new treatment, he said.”

The study's co-authors, Hualin Zhou and Richard Premont from Case Western Reserve School of Medicine and University Hospitals, along with students Zack Grimmett and Nicholas Venetos from the university’s Medical Scientist Training Program, contributed significantly to the research endeavor.

Nitric oxide has long been implicated in various diseases, including Alzheimer's, cancer, heart failure, and diabetes, with excessive nitric oxide binding to key proteins believed to play a role in disease onset and progression. Stamler underscored the importance of enzymes involved in nitric oxide attachment, particularly in the context of diabetes and other related conditions.

Diabetes, characterized by the body's diminished response to insulin, leads to elevated blood sugar levels, contributing to severe health complications over time, including heart disease, vision impairment, and kidney dysfunction. Despite the prevalence of diabetes-related health issues, the underlying mechanisms behind insulin resistance remain poorly understood.

Stamler highlighted the challenge of targeting nitric oxide due to its reactivity and lack of specificity. However, the identification of enzymes like SCAN opens up new avenues for therapeutic interventions.

"This paper shows that dedicated enzymes mediate the many effects of nitric oxide. Here, we discover an enzyme that puts nitric oxide on the insulin receptor to control insulin. Too much enzyme activity causes diabetes. But a case is made for many enzymes putting nitric oxide on many proteins, and, thus, new treatments for many diseases," he explained.

Moving forward, the research team aims to explore the development of medications targeting the SCAN enzyme, offering a potential breakthrough in diabetes treatment and potentially other nitric oxide-related diseases.

This discovery marks a significant step towards unraveling the complexities of diabetes and holds promise for the future of therapeutic interventions in related conditions.

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