Diabetes, metabolic syndrome in mice treated with novel compound

A new compound developed by scientists can improve metabolic syndrome in multiple ways, according to a study in mice by researchers at Washington University School of Medicine in St.
Louis
.

Metabolic syndrome is an increasingly common disorder that often co-occurs and includes type 2 diabetes, high cholesterol, fat buildup in the liver, and excess body fat, especially around the waist

The research was published in the journal Nature Communications
.

When testing a compound called SN-401, the researchers found that it treats diabetes by improving the ability of the pancreas to secrete insulin and the ability of other tissues to use insulin to more efficiently remove sugar from the blood
.

To optimize the treatment, the researchers fine-tuned the compound -- creating a class of related compounds -- based on studies of a key protein in SWELL1 (also called LRRC8a)

"Our goal is to develop better treatments for cardiovascular disease, including diabetes and metabolic syndrome, which are major risk factors for worsening heart and blood vessel problems," said senior author Rajan Sah, MD, associate professor of medicine
.

"We have many treatments for diabetes, but even with these treatments, cardiovascular disease remains the leading cause of death in people with type 2 diabetes

The protein Sah and his colleagues studied is called SWELL1 because its role is to sense the size or volume of cells
.

Their new study shows that the protein also helps control insulin secretion from the pancreas and improves insulin sensitivity, including skeletal muscle and adipose tissue, the body's fat storage

Surprisingly, the researchers found that swell can perform these two seemingly independent tasks at the same time because the protein has a previously unknown dual life
.

It acts as a signaling molecule that initiates cellular tasks that control how cells use insulin and prompts the pancreas to secrete insulin into the bloodstream

"This protein, called SWELL1, has a sort of dual personality," Sah said
.

The compound binds to the swell in a way that stabilizes a protein complex that enhances expression and signaling in a variety of tissues, including fat, skeletal muscle, liver, Vascular lining and pancreatic islet cells

Sah and his colleagues found that the SN-401 compound improved multiple aspects of metabolic syndrome in two groups of mice, each of which developed diabetes for a different cause, one due to genetic predisposition and the other due to a high-fat diet
.

In addition to improving insulin sensitivity and secretion, treatment with this compound can also improve blood sugar levels and reduce fat accumulation in the liver

The researchers further showed that the compound did not have a large effect on blood sugar in healthy mice, which is important for its possible future as a treatment
.
Current medications for diabetes can cause blood sugar levels to go too low
.
Evidence suggests that this compound doesn't lower blood sugar when it's not needed
.