Overweight and obese people have a higher risk of diabetes, but the exact mechanism is still not well understood.
A new study at Washington University School of Medicine in St. Louis may help explain how being overweight can contribute to diabetes and may provide researchers with a target to help prevent or delay diabetes in some people at risk. The findings suggest that many people with high insulin levels – an early marker of diabetes risk – also have a defect in an enzyme important for processing an important fatty acid from the diet. to drink.
The study was published January 11 in the journal Cell Metabolism.
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“Between 30 million and 40 million people in the United States have Type 2 diabetes, and another 90 million to 100 million have risk factors that make them more likely to develop diabetes.” type 2 diabetes in the future,” says senior investigator Clay F. Semenkovich, MD, director of the Department of Endocrinology, Metabolism & Lipid Research at the School of Medicine, “Many people at risk for diabetes have high insulin levels. , a sign of insulin resistance and a signal that trouble may be on the way. If we can intervene before they actually develop diabetes, we can prevent serious health problems — such as heart disease, chronic kidney disease, nerve damage, vision loss and other problems – in a large number of people.”
When a person has too much body fat, it signals the beta cells in the pancreas to secrete more insulin. When insulin levels are elevated and remain high, the body can become resistant to insulin, and eventually the insulin-secreting beta cells can be damaged, leading to diabetes.
Studying human tissue samples, Semenkovich, Professors Irene E. and Michael M. Karl; first author Guifang Dong, PhD, a senior scientist; Xiaochao Wei, PhD, associate professor of medicine; and other University of Washington researchers have found that overproduction of insulin involves a process called palmitoylation. This is the process by which cells attach fatty acids palmitate to proteins.
Thousands of human proteins can be attached to palmitate, but the researchers found that when this fatty acid is not removed from the protein in beta cells, the end result is diabetes. Examining tissue samples from lean or overweight people, with and without diabetes, the researchers found that the people with diabetes were deficient in an enzyme that removes palmitate from beta cells.
“They secrete too much insulin because the process is malfunctioning and they cannot properly regulate insulin release from beta cells,” explains Semenkovich. “The regulation of insulin release is controlled in part by this palmitoylation.”
Together with colleagues Dr. David W. Piston, Professor Edward W. Mallinckrodt Jr. and Dean of the Department of Cell Biology & Physiology, Maria S. Remedi, PhD, professor of medicine and cell biology & physiology, and Fumihiko Urano, MD, PhD, professor of medicine and pathology & immunology, the team also genetically engineered a mouse that was deficient in an enzyme called APT1, an enzyme responsible for removing palmitate from proteins. The engineered mice went on to develop diabetes.
Since impaired APT1 function contributes to diabetes risk, the researchers worked with the university’s Center for Drug Discovery to screen for and identify compounds that may increase activity. of the enzyme APT1.
“We have found some candidate drugs and we are pursuing them,” said Semenkovich. “We think that by increasing the activity of APT1, we can reverse this process and potentially prevent people at risk from developing diabetes.”
While he says the new findings identifying APT1 as a target is an important step, Semenkovich explains that APT1 is just one therapeutic target among many.
“There are a number of ways that Type 2 diabetes can develop,” he said. “This enzyme isn’t the answer, but it is an answer, and it looks like we have some promising tools that could help some people with diabetes develop diabetes.”
This story was published from the wire dealer’s feed without text modification.
