Scientists Think They’ve Found a New Cause of Type 2 Diabetes

Written by Science Alert on January 7, 2024. Posted in Current News

More than half a billion people worldwide are affected by type 2 diabetes, and yet researchers still don’t know what’s behind the condition’s breakdown in insulin functionality.

Researchers from Case Western Reserve University in the US have now pulled back the molecular curtain and figured out why insulin, the hormone that maintains stable blood sugar, often stops working at its full effect.

The principal investigator, Jonathan Stamler, is widely acclaimed for the discovery of S-nitrosylation, which is the process that turns nitric oxide (NO) into a ubiquitous messenger molecule capable of sharing information between cells. It’s kind of like putting a stamp on a letter.

Nitric oxide is produced in almost all cell types and tissues, and it plays a crucial role in the functioning of the nervous system, the immune system, and in blood vessel dilation. What’s more, dysregulation of S-nitrosylation is increasingly found to be associated with a number of health conditions, such as multiple sclerosis, Parkinson’s disease, sickle cell disease, and asthma.

Only recently, however, has NO been linked to aspects of the body’s metabolism.

Stamler and his colleagues previously suspected that the role of NO is overlooked in some types of diabetes, and now, they have the evidence to support their hypothesis.

The team at Case Western Reserve has discovered a novel enzyme, called SCAN (SNO-CoA-assisted nitrosylase), that plays a role in S-nitrosylation. It helps attach NO to its target proteins, such as the receptors on insulin.

In humans and mice with resistance to insulin, SCAN activity appears to be heightened.

In mouse models of diabetes, Stamler and his colleagues found that when SCAN was inhibited, the animals did not show the classic symptoms.

Together, the findings suggest that type II diabetes may be driven by an overabundance of NO attaching to proteins like insulin. Any enzymes, like SCAN, that work to attach NO to its receptors could, therefore, be useful targets in future research.

Stamler hopes that by blocking the SCAN enzyme, scientists may find new treatments for at least some types of diabetes.

Type I diabetes, however, is caused by a sheer lack of insulin production, and this would probably require a different avenue of treatment.

“This paper shows that dedicated enzymes mediate the many effects of nitric oxide,” explains Stamler.

“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.”

The study was published in Cell.

Source: Science Alert

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