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U Researcher Identifies Possible Cause of Type 2 Diabetes

U Researcher Identifies Possible Cause of Type 2 Diabetes
Photographer: Raymond Phang

A team of researchers from around the world, including chairman of the U’s Department of Nutrition and Integrative Physiology, Scott Summers, recently published a study that found a family of chemicals that may increase a person’s risk of developing type 2 diabetes.

When food enters the body, the molecules are broken down and used to make the chemicals that bodies require to function. One of the most well-known molecules from food are fatty acids. The body uses excess fatty acid molecules to make another molecule called triglycerides, which is what human body fat is composed of.

Some fatty acids, however, are used to make a toxic set of chemicals called ceramides.

The findings were based on experiments performed on both human cells and mice.

Summers, the senior author, said mice were used because they “are a pretty good model of pre-diabetes, and many of the discoveries made in that organism have proven relevant to human disease.” He also explained that the genetic engineering is done for the study “is most commonly done in mice.”

Researchers found that increased amounts of ceramides in both human cells and living mice “caused them to become unresponsive to insulin and develop impairments in their ability to burn calories,” according to the U’s press release regarding the study. The mice saw an increased likelihood for development of diabetes, as well as other related diseases because the ceramides caused body fat to stop storing the cells that contain triglycerides. Those cells then escape into the bloodstream and ultimately damage other parts of the body.

When researchers prevented mice from making ceramides in their bodies, they found the mice were better at regulating their blood glucose levels and were less likely to develop resistance to insulin. This means that they were at a decreased risk for development of diabetes — a disease characterized by the inability to maintain healthy blood glucose levels due to an insensitivity to insulin.

The results of the study show that ceramides profoundly influence how susceptible mice are to diabetes and other related diseases.

The researchers are now directing their attention to finding ways to control the genes that influence to ceramide production. They hope that this could lower the risk of, or even prevent, humans from developing type 2 diabetes.

Summers said that, since they’ve identified the genes in question, a follow-up study will include “people with and without the altered gene.” It will also “mimic the mutation in mice so that we can do more of a mechanistic evaluation.” They want to “evaluate exactly how the mutation alters gene function,” which “couldn’t [be done] in people.”

Summers said researching diabetes is his life’s work. When he was 14 years old, his father was diagnosed with a late-onset form of the disease. “He had an odd form of diabetes, as he was exceptionally fit and athletic,” he said. This study can explain why that’s possible — ceramide production is genetically regulated, meaning that some people can store fatty acids properly while others cannot, leading to the development of diseases such as diabetes.

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