video: The animation explains that insulin treatment of patients with diabetes reduces glucose levels, but it causes significant direct damage on the human arteries by activating oxidative stress. Treating patients with a DPP4 inhibitor "sensitizes" the human arteries and makes them respond in the opposite way to insulin, i.e. insulin reduces vascular oxidative stress, becoming from a detrimental to a beneficial intervention. This means that treatment with DPP4 inhibitors may allow insulin treatment to reduce the risk for heart attacks and strokes in diabetics. This material relates to a paper that appeared in the Apr. 29, 2020, issue of Science Translational Medicine, published by AAAS. The paper, by I. Akoumianakis at University of Oxford in Oxford, UK; and colleagues was titled, "Insulin-induced vascular redox dysregulation in human atherosclerosis is ameliorated by dipeptidyl peptidase 4 inhibition." view more
Credit: [Credit: Oxford Translational Cardiovascular Research Group]
By studying blood vessel tissue from 674 patients, a research team has discovered how insulin contributes to the dysfunction of blood vessels in atherosclerosis, one of the most common chronic health conditions worldwide. Their research explains why insulin treatment fails to treat vessel damage in patients with diabetes and highlights a promising alternative therapy to correct insulin signaling and protect blood vessels. Insulin is a fundamental hormone in the body, as it regulates processes ranging from blood sugar control to chemical reactions in the cardiovascular system. Patients with type 2 diabetes often develop other chronic conditions such as heart disease and atherosclerosis, and research suggests that abnormal insulin signaling may be to blame. However, lowering blood sugar with insulin-like compounds has failed to reduce cardiovascular risk in diabetic patients. To understand why, Ioannis Akoumianakis and colleagues examined blood vessels from 674 patients with atherosclerosis who underwent coronary artery bypass surgery. They discovered that the patients' blood vessels were resistant to insulin - which normally controls the tone of blood vessels - and showed elevated levels of stress from harmful oxygen molecules. Instead, high levels of insulin correlated with more dysfunction in cells that line the insides of blood vessels. Treating the vessels with an experimental inhibitor of the enzyme DPP4 reduced oxidative stress and restored normal insulin activity, and chronic treatment with a DPP4 inhibitor reversed the damaging vascular effects of insulin in patients and in mice fed a high-fat diet. The authors conclude that future trials should explore the possibility of combining insulin treatment with DPP4 inhibitors to mitigate vessel damage in patients with atherosclerosis.
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Journal
Science Translational Medicine