OU Health Harold Hamm Diabetes Researchers Discover Cancer Drug’s Ability to Lower Blood Sugar

Researchers at OU Health Harold Hamm Diabetes Center have discovered that a drug developed to suppress cancerous tumors also has the ability to lower blood sugar levels that were elevated due to obesity and Type 2 diabetes. The study is published in the prestigious journal Proceedings of the National Academy of Sciences.

Repurposing a drug to treat a different disease is not only an innovative leap forward, but because the drug has already been tested for safety, the timeline to its new use could be shortened if research continues to prove its benefit. In addition, the drug appears to be effective at lowering blood sugar without requiring a reduction in body weight.

Harold Hamm Diabetes Center researcher Tiangang Li, Ph.D., made the discovery of how the drug lowers blood sugar. He is the lead author of the study along with co-author Jed Friedman, Ph.D., director of Harold Hamm Diabetes Center.

“It’s very exciting to see emerging evidence that this drug could be repurposed,” said Li, who holds the Harold Hamm Chair in Adult Diabetes Research. “It is a new drug for cancer treatment, and we were able to find that it has a beneficial effect on insulin resistance.”

Insulin resistance — when the body’s cells do not respond normally to insulin — is a major underlying cause of Type 2 diabetes. Insulin is the most important hormone for normalizing blood glucose levels, working primarily through the liver and skeletal muscles. If the cells don’t respond properly to insulin, blood sugar levels rise.

This study focused on insulin resistance in the liver. One of the reasons the liver becomes resistant to insulin is that a particular protein degrades, which in turn impairs the liver’s ability to lower blood sugar. Li discovered that the cancer drug, known as MLN4924, prevents degradation of the protein, thereby restoring liver insulin sensitivity and lowering blood sugar.

Most of the current drugs used to treat diabetes work either on the pancreas, kidney, or the gastrointestinal system, Friedman said. The cancer drug is unique in that it works through the liver, which means it may hold the potential to control blood sugar on its own or in addition to other drugs, he said.

The cancer drug is also novel in that it appears to work without weight loss being necessary. Typically, when patients are diagnosed with diabetes, they are encouraged to change their nutrition and lifestyle in order to lose 5-10% of their body weight. By losing weight, patients become metabolically healthier and, often, require less insulin. However, sustained improvement is contingent upon patients continuing to exercise and eat well.

“This drug preserves a pathway for suppressing glucose levels that normally goes away as people develop diabetes,” Friedman said. “That’s critical for Type 2 diabetes.”

The study’s findings are also important for conditions that often accompany diabetes, such as non-alcoholic fatty liver disease (NAFLD), Friedman said. Most people who are overweight or obese have some level of NAFLD. In addition to lowering blood sugar, the drug also reduced symptoms of NAFLD during the study. Because advanced NAFLD carries a risk of liver cancer, the drug potentially reduces that risk.

The University of Oklahoma Health Sciences Center has applied for a patent on the drug’s ability to lower blood glucose, and is pursuing opportunities to modify the drug to make it even more effective for treating Type 2 diabetes. Friedman said the research team also has applied for a National Institutes of Health grant to further study how the drug works.

“This serves as a reminder of the importance of basic science research for discovering new drug targets and advancing the research all the way to humans,” Friedman said. “That is the focus of the Harold Hamm Diabetes Center — to translate findings from the research bench to the patient’s bedside.”