A study in mice — led by researchers at Washington University School of Medicine in St. Louis — shows that a new class of compounds the scientists developed can improve multiple aspects of metabolic syndrome. An increasingly common group of conditions that often occur together, metabolic syndrome includes type 2 diabetes, high cholesterol, fat buildup in the liver, and excess body fat, especially around the waist. This syndrome often leads to cardiovascular disease, the leading cause of death worldwide.
The study is published in the journal Nature Communications.
Testing one of the compounds referred to as SN-401, the researchers found it treats diabetes by improving the ability of the pancreas to secrete insulin and boosting the ability of other tissues to utilize that insulin to more effectively remove sugar from the bloodstream. In an effort to optimize the treatment, the researchers fine-tuned the compound — creating a class of related compounds — based on their studies of a key protein called SWELL1 (also LRRC8a). The gradual decline of this protein may have a central role in the development of diabetes and other aspects of metabolic syndrome.
“Our goal is to develop better therapies for cardiovascular disease, including diabetes and metabolic syndrome, which are major risk factors for worsening heart and vascular problems,” said senior author Rajan Sah, MD, PhD, an associate professor of medicine. “We have many treatments for diabetes, but even with those therapies, cardiovascular disease remains a leading cause of death among patients with type 2 diabetes. There is a need for new treatments that work differently from the current standard-of-care therapies.”
The protein Sah and his colleagues studied is called SWELL1 because of its role in sensing the size or volume of cells. Their new research reveals that the protein also helps to control insulin secretion from the pancreas and improve insulin sensitivity, including in skeletal muscle and adipose tissue, the body’s fat stores.