A study published today has discovered a warning sign that indicates an increased risk of developing Diabetes in the future.
Approximately 30-40 million Americans currently have Type 2 diabetes, with an additional 90-100 million individuals having risk factors that increase their chances of developing the condition in the future.
Individuals who are at risk for diabetes often have higher levels of insulin, which is an indication of insulin resistance and can signal that diabetes is likely to develop. If early interventions could be made before the onset of diabetes, it could potentially prevent several serious health issues such as heart disease, chronic kidney disease, nerve damage, vision loss, and other complications in a large number of people.
It is widely known that being overweight or obese increases the likelihood of developing diabetes, however, the mechanisms behind this correlation remain unclear.
The Washington University School of Medicine in St. Louis has conducted a new study that aims to shed light on how extra weight contributes to diabetes and may aid in identifying potential targets for preventing or delaying diabetes in high-risk individuals.
The results show that many people with high levels of insulin, which is an early sign of diabetes risk, also have problems with an enzyme that is needed to break down a key fatty acid from food.
The study was published in the journal Cell Metabolism today.
Excess body fat prompts beta cells in the pancreas to produce more insulin. When insulin levels are consistently high, the body becomes resistant to insulin, ultimately leading to the failure of beta cells and resulting in diabetes.
Through the examination of human tissue samples, researchers from Washington University led by Professor Semenkovich, Guifang Dong, Xiaochao Wei, and other team members discovered that the overproduction of insulin is associated with a process called palmitoylation. This is the attachment of the fatty acid palmitate to proteins within the cells.
The attachment of a fatty acid called palmitate to thousands of human proteins is possible, however, the researchers found that when palmitate is not removed from beta cell proteins it leads to diabetes. Through examination of tissue samples taken from individuals who varied in weight and whether they have diabetes or not, it was found that those with diabetes had a lack of an enzyme responsible for removing palmitate from beta cells.
“They hyper-secrete insulin because this process goes awry, and they can’t appropriately regulate the release of insulin from beta cells,” explains senior investigator Clay F. Semenkovich. “Regulating insulin release is controlled in part by this palmitoylation process.”
The study team also genetically modified a mouse that was deficient in the enzyme known as APT1, which is in charge of removing palmitate from proteins, along with colleagues David W. Piston, PhD, the Edward W. Mallinckrodt Jr. Professor and head of the Department of Cell Biology & Physiology, Maria S. Remedi, PhD, a professor of medicine and of cell biology & physiology, and Fumihiko Urano, MD, PhD. The genetically modified animals later developed diabetes.
Because poor APT1 function is related to diabetes risk, researchers collaborated with the university’s Center for Drug Discovery to screen and find drugs that potentially boost APT1 enzyme activity.
“We’ve found several candidate drugs, and we’re pursuing those,” Semenkovich adds. “We think that by increasing APT1 activity, we might reverse this process and potentially prevent people at risk from progressing to diabetes.”
Semenkovich noted that APT1 is merely one of several therapeutic targets, despite his claim that the recent discoveries identifying APT1 as a target constitute a significant step.
“There are several ways that Type 2 diabetes may develop,” he adds. “This enzyme is not the answer, but it’s an answer, and it appears we have some promising tools that might keep some people with prediabetes from developing diabetes.”
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