New compound improves insulin secretion and lowers blood sugar in treated mice

February 16, 2022

An experimental drug developed by scientists at Washington University School of Medicine in St. Louis was reported to improve key aspects of metabolic syndrome, which includes diseases such as type 2 diabetes and high cholesterol. In preclinical studies, the drug was observed to increase the expression of a protein that influences insulin signaling and uptake in cells – the gradual decline of this protein is thought to lead to the development of type 2 diabetes and other aspects of metabolic syndrome.

Associate professor of medicine Dr. Rajan Sah and colleagues studied the protein, SWELL1, and revealed it helps to control insulin secretion from pancreatic cells and improve insulin sensitivity, including in skeletal muscle and adipose tissue, the body’s fat stores. So, his team developed a molecule called SN-401 to augment SWELL1 expression in the hopes it could normalise metabolic function in diabetic mice.

In addition to improving insulin sensitivity and secretion, treatment with an injected form of the SN-401 compound also improved the animals’ blood sugar levels and reduced fat buildup in the liver. Most significantly, the compound did not impact blood sugar levels in situations when it does not need to.

Dr. Sah has recently formed a startup to investigate commercial drug outcomes from his SN-401 research. His team concluded: “The current study provides an initial proof-of-concept for pharmacological induction of SWELL1 signaling using SWELL1 modulators (SN-40X) to treat metabolic diseases at multiple homeostatic nodes, including adipose, skeletal muscle, liver, and pancreatic β-cell, whereby SN-40X compounds function to restore both insulin sensitivity and insulin secretion.

“Hence, SN-401 may represent a tool compound from which a novel drug class may be derived to treat type 2 diabetes, NASH, and other metabolic diseases.”

[NASH is a severe form of nonalcoholic fatty liver disease.]

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