In a new study, researchers from the Scripps Research Institute in the U.S., with colleagues from the Ulsan National Institute of Science and Technology (UNIST) in South Korea, Hyndai Pharm Co., and Seoul National University, revealed that Novartis’ imatinib (Gleevec), a drug approved for the treatment of cancers such as acute myeloid leukemia (AML), may also act as a therapeutic agent for insulin resistance and type 2 diabetes.
The research article, “PPARγ antagonist Gleevec improves insulin sensitivity and promotes the browning of white adipose tissue,” was published in Diabetes, an American Diabetes Association journal.
Thiazolidinediones, or TZDs, a class of insulin-sensitizing drugs used for the treatment of type 2 diabetes, are selective agonists of peroxisome proliferator-activated receptor γ (PPARγ), molecules that play a central role in the body’s metabolism of glucose, storage of fat, and immune and inflammatory responses.
Despite their efficacy at improving glucose uptake by skeletal muscle and other tissues, the risk of adverse side effects has led to these drugs being withdrawn from the market. These events have led researchers to study and develop new medications with fewer side effects.
The research team observed that blocking phosphorylation of PPARγ had anti-diabetic effects. Scientists discovered, through high-throughput phosphorylation screening, that Gleevec blocks CDK5-mediated PPARγ phosphorylation as a PPARγ antagonist ligand.
In high fat-fed mice, Gleevec was found to improve insulin sensitivity without causing severe side effects associated with other drugs with the same mechanism of action, ameliorated inflammation in adipose tissue, and increased browning of white adipose tissue and energy expenditure.
“Although studies have shown that Gleevec treatment may show improved insulin sensitivity and decrease blood glucose in patients with known diabetes, the exact cause hasn’t been proven yet,” the study’s leader, Prof. Jang Hyun Choi of the Department of Biological Sciences at UNIST, said in a news release. “Through this research, we discovered Gleevec, which is used in leukemia medications, can inhibit the phosphorylation of PPARγ.”
The researchers believe that the findings demonstrate that Gleevec has greater beneficial effects on both glucose and lipid metabolism and energy homeostasis by blocking PPARγ phosphorylation and, as such, it could be considered a novel therapeutic agent for insulin resistance and type 2 diabetes.