PhotoOver 29 million people in the U.S. have diabetes, and over eight million who have it are undiagnosed, according to a 2014 statistical analysis. Although the disease affects so many, it has been hard for scientists and researchers to nail down a cure. This is due, in part, to the fact that the disease can take different forms, and there are still some things that researchers do not know about them.

However, a recent study conducted at the University of Pennsylvania has shed some light on type 2 diabetes. Researchers at the Perelman School of Medicine believe that they have finally found the cause of insulin resistance, which is characteristic of this particular type of the disease.

Excess fat

Many people attribute insulin resistance to fluctuating sugar levels in the body, but researchers say that it also has to do with the amount of fat in the body. In particular, too much fat inside of skeletal muscle is one main cause of insulin resistance.

With this in mind, scientists went about trying to find out how excess fat could be removed from skeletal muscle. If this fat could be removed, they reasoned, then it would also be possible to prevent insulin resistance from occurring. But in order to do that, there were some questions that had to be answered first.

“This research sought to answer a few large questions. . . How does fat get into skeletal muscle? And how is the elevation of certain amino acids in people with diabetes related to insulin resistance?” asked Dr. Zoltan Arany, senior author of the study. “We have appreciated for over ten years that diabetes is accompanied by elevations in the blood of branched-chain amino acids, which humans can only obtain in their diet. However, we didn’t understand how this could cause insulin resistance and diabetes. How is elevated blood sugar related to these amino acids?”

New way to treat diabetes

In order to answer these questions, Dr. Arany and his team began examining amino acids and what happened when they broke down. They found that when these compounds broke down, a byproduct called 3-HIB was created. After being secreted by muscle cells, 3-HIB activated certain cells which resulted in more fat being stored in skeletal muscle tissue.

Researchers observed this phenomenon in mice and saw that when it happened it led to insulin resistance. By blocking 3-HIB from synthesizing, researchers were able to keep excess fat from going to the skeletal muscle and insulin resistance was no longer a problem.

Dr. Arany is quick to note that 3-HIB byproducts are also plentiful in humans who have type-2 diabetes, so although there will need to be more research to prove that there is a link, he is confident that one may be discovered in the future.

“The discovery of this novel pathway – the way the body breaks down these amino acids that drives more fat into the muscles – opens new avenues for future research on insulin resistance, and introduces a conceptually entirely new way to target treatment for diabetes,” he said.

The full study has been published in Nature Medicine


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