Cancer Drug Shows Promise Treating Type 2 Diabetes


TZD-based medicines effectively improve glucose uptake.

A popular drug used for the treatment of chronic myeloid leukemia (CML) offers hope treating patients with type 2 diabetes, according to a recent study.

The anti-cancer drug imatinib (Gleevac) has been found to lower the level of insulin resistance through the control PPARy. This action reduces the risk of hyperglycemia and obesity.

“Although TZD-based medicines work effectively at improving glucose uptake by skeletal muscle and other peripheral tissues, due to increased risk of adverse effects they have been withdrawn from the market,” said lead researcher Jang Hyun Choi. “In order to develop new type of medication that have fewer side effects, we have discovered a new compound that can maintain stable blood sugar levels.”

TZDs are a therapeutic class that act as selective agonists for PPARy and plays a key role in how the body metabolizes glucose, stores fat, and controls immune and inflammatory responses.

A study published in Diabetes found that the phosphorylation of PPARy was closely related to the development of diabetes. The study revealed that when phosphoric acid is removed from PPARy, it had an anti-diabetic effect.

By using a newly developed chemical screening procedure, researchers sought to determine if phosphoric acid binds to PPARy. The results of the study showed that Gleevec blocks CDK5-mediated PPARy phosphorylation devoid of classical agonism as a PPARy antagonist ligand.

“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,” Choi said. “Through this research, we discovered Gleevec, which is used in leukemia medications, can inhibit the phosphorylation of PPARγ.”

Mice on a high-fat diet administered Gleevec demonstrated improved insulin sensitivity without causing severe side effects typically seen with other PPARy-targeting drugs.

Gleevec also reduced lipogenic and gluconeogenic gene expression in the liver and improved inflammation in adipose tissues. Additionally, Gleevec increased the browning of white adipose tissue (WAT) and energy expenditure.

“Taken together, Gleevec exhibits greater beneficial effects on both glucose/lipid metabolism and energy homeostasis by blocking PPARγ phosphorylation,” the researchers wrote. “These data illustrate that Gleevec could be a novel therapeutic agent for use in insulin resistance and type 2 diabetes.”

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