This discovery could lead to a breakthrough new treatment for metabolic disorders-ScienceDaily

Eliminating old dysfunctional cells in human fat also alleviates the signs of diabetes, according to UConn Health researchers. This discovery may lead to new treatments for type 2 diabetes and other metabolic disorders.

The cells in your body are constantly renewing themselves, and as new cells are born, old cells age and die. But sometimes the process doesn’t work. Occasionally damaged cells remain. Called senescent cells, they are hanging around and adversely affect other cells nearby. These adverse effects change the way adjacent cells process sugars and proteins, causing metabolic problems.

Type 2 diabetes is the most common metabolic disease in the United States. According to the Centers for Disease Control and Prevention (CDC), about 34 million people, or one in ten Americans, suffer from the disease. Most people with diabetes have insulin resistance associated with obesity, lack of exercise, and a poor diet. However, according to new discoveries by Ming Xu and his colleagues at UConn Health School of Medicine, it is also related to senescent cells in people’s body fat. And clearing those senescent cells seems to stop the diabetic behavior of obese mice, they report in the November 22 issue of Cellular Metabolism. Ming Xu, an assistant professor at UConn Center on Aging and the Department of Genetics and Genomics at UConn Health, led the research, with UConn Health researchers Richao Wang and Binsheng Wang as key contributors. Reducing the negative effects of fat on metabolism has been a dramatic result, the researchers said. If the treatment works well in humans, it will be a breakthrough treatment for diabetes.

Xu and his colleagues tested the efficacy of the combination of the experimental drugs dasatinib and quercetin. Dasatinib and quercetin have already been shown to extend the lifespan and health of older mice. In this study, they found that these drugs could kill senescent cells from cultures of human adipose tissue. The tissue was donated by an obese individual known to have a metabolic disorder. Without treatment, human adipose tissue caused metabolic problems in immunocompromised mice. After treatment with dasatinib and quercetin, the harmful effects of adipose tissue have almost disappeared.

“These medicines can make human fat healthy, and it may be great,” says Xu. “The results were very impressive and paved the way for potential clinical trials.”

UConn Health and Mayo Clinic’s Xu and his colleagues are currently using a combination of dasatinib and quercetin in clinical trials to see if the drug can improve type 2 diabetes in human patients. “Although these preclinical results were very promising, large-scale clinical trials are absolutely important to investigate the efficacy and safety of these drugs in humans prior to clinical use,” Xu emphasizes. Did.

The research team is also focusing on previously unexplored senescent cell populations. These senescent cells express high levels of p21, a cyclin-dependent kinase inhibitor and one of the key markers of cellular senescence. By using a newly developed mouse model, Xu’s team found that clearance of these senescent cells was effective in both delaying the onset of diabetes in obese mice and alleviating the onset of diabetic symptoms. I showed that there is. According to Xu, previous studies focused on a variety of cell markers, but the effect of removing cells that are highly p21-expressing was so pronounced in alleviating diabetes. We need to pay more attention.

This research was primarily funded by the National Institute of Aging, the Regenerative Medicine Initiative Diabetes Career Development Award from the Mayo Clinic, the Esperance Fellowship in Personal Nutrition, and the American Federation of Aging Research.

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material Provided by University of Connecticut.. Original written by Kim Krieger. Note: Content can be edited in style and length.

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