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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Science Translational Medicine