News

More than 30 million Americans have diabetes, according to the American Diabetes Association. A recent breakthrough by a Harvard School of Medicine research team has now shown that insulin may also impact the body in a unique way.

The study, led by Dr. Thomas Michel, of Harvard Medical School and Brigham and Women’s Hospital, was recently published in Free Radical Biology and Medicine, a journal of the Society for Redox Biology and Medicine.

This new discovery unveiled an entirely unexpected mechanism whereby insulin-dependent generation of hydrogen peroxide (H₂O₂) in cardiac myocytes controls heart contractility and critical cell signaling pathways.  These research findings have direct implications for our understanding of diabetic cardiomyopathy, which is a major cause of morbidity and mortality for patients with diabetes.

Dr. Michel, a Professor of Medicine and Biochemistry and an SfRBM member said, “These experiments reveal a new and unexpected role of H₂O₂ as a critical mediator of the physiological effects of insulin in the heart.  We usually think of H₂O₂ as a harmful molecule that can cause pathological oxidative stress in diabetes and other diseases.  Our recent discoveries help to establish that H₂O₂ actually plays a central role in modulating insulin action in the normal heart.  We now need to more fully understand the factors that govern the transition from the physiological roles of H₂O₂ in normal cells to the pathological roles of H₂O₂ and related  molecules in disease states.”

Michel’s team first observed that insulin treatment attenuated the usual response seen when adrenaline-like drugs are used to stimulate the contraction of cardiac myocytes isolated from mice. Benjamin Steinhorn, a Harvard MD-PhD student, along with postdoctoral fellow Juliano Sartoretto, used novel biosensor methods and genetic approaches to demonstrate that the attenuated contractile response was due to cellular generation of H₂O₂ by two distinct but closely-related enzymes, NOX2 and NOX4, following insulin treatment. However, these effects of insulin were absent in cardiac myocytes isolated from diabetic mice. These findings suggest that insulin resistance in the diabetic heart may lead to deleterious potentiation of contractile responses and promote the development of heart failure.