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Scientists Find Accidental Cure for Type 2 Diabetes: Imatinib

AJMC Staff
The cancer drug, best known as a game-changer for chronic myeloid leukemia, lowers insulin resistance through a similar mechanism as TZDs without the negative effects.
The cancer drug imatinib—marketed as Gleevec and known as a game-changer for conditions like chronic myeloid leukemia—may prove the same in type 2 diabetes (T2D), according to a study published recently in Diabetes.

Researchers in the United States and in South Korea found that imatinib controls PPARy, which lowers the level insulin resistance and thus reduces the risk of hyperglycemia and obesity. PPARy affects how the body metabolizes glucoses and stores fat, and also affects immune and inflammatory responses.

This same mechanism of action was at work with the class of drugs known as the thiazolidinediones or TZDs, the most famous of which was rosiglitazone, or Avandia. Risks reported in the New England Journal of Medicine forced Avandia off the market and others in the class followed, although a followed up trial exonerated the drug.

The study team noted that the phosphorylation of PPARy is related to developing diabetes; taking away the phosphoric acid from PPARy has an anti-diabetic effect. In the laboratory, the team found that imatinib had the same “blocking” effect on PPARy phosphorylation but without some of the effects seen in the TZDs.

Researchers can see the “what” but don’t understand the “why” just yet. “Although studies have shown that (imatinib) treatment may show improved insulin sensitivity and decreased blood glucose in patients with known diabetes, the exact cause hasn’t been proven yet,” said Jang Hyun Choi, PhD, assistant professor. Ulsan National Institute of Science and Technology (UNIST), in South Korea.

The team tested imatinib in mice that had been fed a high-fat diet. The drug improved insulin sensitivity without causing severe side effects that had been observed with the TZDs.

Reference

Choi SS, Kim ES, Jung JE, et al. PPARy antagonist Gleevec improves insulin sensitivity and promotes the browning of white adipose tissue Diabetes. 2016; 65(4):829 doi: 10.2337/db15-1382.

 
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