Leukemia drugs may cure type 2 diabetes. New research reveals that the cancer drug Imatinib (Gleevec), which combats tumors by shutting off an enzyme that turns cells cancerous and causes them to multiply, can successfully treat type 2 diabetes.
Scientists from the Scripps Research Institute and Seoul National University have discovered for the first time that blocking phosphorylation of peroxisome proliferator-activated receptors decreases the risk of hyperglycemia and obesity by lowering insulin resistance.
Researchers noted that the Imatinib works like thiazolidinediones or TZD-based drugs in treating diabetes, but without the harmful side effects. TZD-based drugs have been shown to control how the body metabolizes glucose, stores fat and controls inflammatory responses via the PPARy pathway.
"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glucose uptake by skeletal muscle and other peripheral tissues, due to increased risk of adverse effects they have been withdrawn from the market," said professor Jang Hyun Choi.
"In order to develop new type of medication that [has] fewer side effects, we have discovered a new compound that can maintain stable blood sugar levels," added Choi, the lead researcher of the current study and professor of the School of Life Sciences at Ulsan National Institute of Science and Technology.
Previous studies revealed that TZD-based drugs increase the risk of weight gain, macular edema, heart failure and increased bone fracture as well as hypoglycemia.
Findings from the latest study revealed that Imatinib helped improve symptoms of type 2 diabetes by successfully blocking cyclin-dependent kinase 5 mediated PPARγ phosphorylation. Mice fed a high-fat diet also showed substantial improvement in insulin sensitivity when given Imatinib. Further analysis revealed that Imatinib significantly increased browning of harmful white adipose tissue as well as lower lipogenic and gluconeogenic gene expression in the liver.
"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," said Choi. "Through this research, we discovered Gleevec, which is used in leukemia medications, can inhibit the phosphorylation of PPARγ."
"Taken together, Gleevec exhibits greater beneficial effects on both glucose/lipid metabolism and energy homeostasis by blocking PPARγ phosphorylation. These data illustrate that Gleevec could be a novel therapeutic agent for use in insulin resistance and type 2 diabetes," researchers wrote in the study.
The findings are published in the journal Diabetes.
