Study reverses long-held ideas about the relationship between diabetes, fat and cardiovascular disease


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A major risk factor for diabetes, insulin resistance occurs when the body’s cells do not respond to insulin and cannot use the glucose (sugar) in the bloodstream. The condition is known to increase the risk of cardiovascular disease and atherosclerosis, a buildup of fats inside blood vessels that can restrict blood flow to body tissues. The exact mechanism by which insulin and the cells lining the vascular walls interact with each other is unknown.

In an article published in circulation investigation, Joslin Diabetes Center scientists describe a series of studies designed to determine the relationship between insulin, fats, and the vascular system. The team, led by George King, MD, chief scientific officer and chief research officer at Joslin, identified a new pathway in which cells lining the blood vessels-I call endothelial cells— Boost the body’s metabolism. In a reversal of scientific dogma, the findings suggest that vascular dysfunction itself may be the cause of the undesirable metabolic changes that can lead to diabetes, and not an effect as previously thought.

“In people with diabetes and insulin resistance, the idea has always been that white fat and inflammation cause blood vessel dysfunction, leading to the prevalence of heart, eye and kidney disease in this patient population.” said King, Dr. Thomas J. Beatson, Jr. Professor of Medicine in the Field of Diabetes at Harvard Medical School. “But we found that blood vessels can have an important control effect here, and that was not known before.”

In addition to being related to abnormalities in the blood vessels, diabetes is also associated with an undesirable decrease in the reserve of brown fatalso called brown adipose tissue. Unlike white fat which primarily stores energy, brown fat burns energy, maintains body temperature, and regulates body weight and metabolism. In a series of experiments using a mouse model of diabetes, King and colleagues found that mice engineered with increased insulin sensitivity in blood vessels alone weighed less than control animals, even when fed a diet rich in insulin. in fats. It turned out that the extra insulin-sensitive mice had more brown fat than the control animals; they also showed less damage to blood vessels.

The team’s further investigation revealed that insulin signals endothelial cells in blood vessels to produce nitrous oxide, which in turn triggers the production of brown fat cells. In the context of insulin resistance, endothelial cells produced less nitrous oxide, a decrease known to increase cardiovascular risk, leading to a decrease in brown fat production. Because brown fat plays such an integral role in regulating the body’s weight and metabolism, smaller stores of brown fat may be a risk factor, not a symptom, of diabetes.

“What we found here is that the endothelial cells that line the blood vessels can have a major controlling effect on how much brown fat develops,” King said. “Nitrous oxide comes from endothelial cells to regulate the amount of brown fat that is produced, and that finding is very exciting because in the past we thought that diabetes caused cardiovascular problems, but that relationship seems to be reversed in this scenario.”

The study findings set the stage for using brown fat and the array of inflammatory hormones and proteins it controls as biomarkers, or signs that doctors can detect, for atherosclerosis or cardiovascular disease. Along the way, with future animal and Clinical studiesthis new information could open the door to an entirely new method of weight management by augmenting brown fat tissues through endothelial enhancement Nitrous oxide production.

“Everything is connected,” King said. “We believe that blood vessels and endothelial cells play an important role not only in the regulation of brown fat, but also in the regulation of metabolism throughout the body. Therefore, these endothelial cells are a key factor in the regulation weight and development diabetes And, as other labs have shown, blood vessels also appear to be an important regulator of brain function. Intervening at the level of endothelial cells could have a major impact on many diseases.”

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More information:
Kyoungmin Park et al, Endothelial Cell Induced Progenitors in Brown Fat to Reduce Atherosclerosis, circulation investigation (2022). DOI: 10.1161/CIRCRESAHA.121.319582

Citation: Study reverses long-held ideas about the relationship between diabetes, fat, and cardiovascular disease (Aug 5, 2022) Retrieved Aug 5, 2022 from -long-held-ideas-relationship -diabetes.html

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