Diabetes is a grave chronic disease which has major dysmetabolic aberrations in carbohydrate, protein and fat metabolism secondary to insulin insufficiency or tissue resistance to its function.1 Macrovascular complications of type 2 diabetes (T2D) include coronary heart disease, cardiomyopathy, arrhythmias, cerebrovascular disease and peripheral artery disease.2 These complications occur through different pathogenetic pathways including hyperglycemia and insulin resistance. Cardiovascular disease is the main reaper of the lives of diabetic patients.3

T2D carries a high risk of atherosclerosis in large vessels. Atheromatous plaques cause arteries to narrow and disrupt blood flow. These plaques may rupture, causing the formation of blood clots, which eventually lead to cardiovascular events.4 Coexistent hypertension, hyperlipidemia and obesity are further reinforcing risk factors. Diabetes has been associated with two- to four fold higher risks of atherosclerotic cardiovascular disease, such as coronary heart disease, ischemic stroke, and peripheral arterial disease.5

Neuregulin 1 (NRG-1) belongs to the epidermal growth factors (EGF) family of proteins. This family comprises four closely related genes, known as NRG1-4, which produce various isoforms that are characterized by the presence of an EGF-like domain. This domain is responsible for the biological activity of the isoforms and their ability to bind to two specific proteins called ErbB3 and ErbB4. NRG-1 is secreted by cells originating from the endothelial, mesenchymal, and neuronal lineages, while ErbB receptors are found in close proximity to the ligand. This allows for local autocrine, paracrine, or even juxtracrine actions to occur.6

NRG-1 was found to be released from the heart endothelial cells. It has regenerative, and antifibrotic effects on the myocardium.7 NRG-1 and the ErbB receptors are expressed in the central nervous system, skeletal muscle, liver, pulmonary cells, enterocytes, and kidney.8

An animal study in rats showed that NRG-1 injection promoted glucose tolerance following an oral glucose load.9 Another study showed that NRG-1 in vitro reduced cholesterol ester accumulation in monocyte-derived macrophages, and administration of recombinant NRG-1 in Apo E deficient mice shrunk the surface area of aortic atheromatous plaques.10

There is a significant unmet clinical need for the identification of the role of NRG-1 in diabetes in humans and its relation to insulin resistance, subclinical atherosclerosis and cardiovascular disease.