It’s been known for a long time that being overweight is associated with a higher risk of type 2 diabetes. The question of why, however, has remained pretty much a mystery.
Now, however, a new study from researchers at Washington University School of Medicine in St. Louis has thrown some light on this baffling question. If further investigation bears out their research, it could mean new strategies in preventing or delaying the onset of diabetes. Or, as lead author Clay F. Semenkovich, MD, explained, “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 likely to develop type 2 diabetes in the future. Many at risk for diabetes have elevated levels of insulin, a hallmark of insulin resistance and a signal that means trouble may be brewing.” The study, entitled “Palmitoylation Couples Insulin Hypersecretion with β Cell Failure in Diabetes,” was published in the science journal Cell Metabolism.
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The role of palmitoylation in diabetes
As the title of the study indicates, the key process is something called “palmitoylation.” The definition of palmitoylation is complicated and rife with technical language, but basically it describes a process in which fatty acids, such as palmitate, attach to proteins in the beta cells in the pancreas. Beta cells in the pancreas create and secrete the hormone insulin, which regulates the amount of glucose in the body, and an excess of body fat stimulates those pancreatic beta cells to produce more insulin than normal. High insulin levels can cause the body to become insulin resistant and also can cause beta cells to fail, triggering diabetes. That is, palmitoylation is involved in the overproduction of insulin, and diabetes results when palmitate is removed from the beta cells.
Furthermore, the research team determined that people with diabetes were deficient in an enzyme that clears palmitate from beta cells. According to Dr. Semenkovich, people with diabetes “hyper-secrete insulin because this process goes awry, and they can’t appropriately regulate the release of insulin from beta cells. Regulating insulin release is controlled in part by this palmitoylation process.” Collaborating with colleagues David W. Piston, PhD, the Edward W. Mallinckrodt Jr. Professor and head of the Department of Cell Biology and Physiology; Maria S. Remedi, PhD, professor of medicine and of cell biology and physiology; and Fumihiko Urano, MD, professor of medicine and of pathology and immunology, Dr. Semenkovich’s research team genetically engineered a mouse that lacked an enzyme called APT1. Sure enough, the mouse developed diabetes.
The untangling of the role that palmitoylation plays in reduced APT1 function prompted the researchers, working with Washington University’s Center for Drug Discovery, to embark on a quest to find something that can boost APT1 action. According to Dr. Semenkovich, “We’ve found several candidate drugs, and we’re pursuing those. We think that by increasing APT1 activity, we might reverse this process and potentially prevent people at risk from progressing to diabetes…. If we could intervene before they actually develop diabetes, we might be able to prevent significant health problems — such as heart disease, chronic kidney disease, nerve damage, vision loss and other problems — in a great number of people.”
Want to learn more about weight management? Read “Seven Ways to Lose Weight,” “Losing Weight Without Feeling Hungry,” and “Tried and True Weight-Loss Techniques.”
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