Grant: Fellowship Award - Hypertension

Type-2 diabetes is the most common metabolic disease in the population, and although the primary cause of this disease is unknown, it is clear that insulin resistance plays a critical role in its pathogenesis. Diabetes has been viewed as a disease caused by deficient secretion of insulin resulting in reduced glucose uptake and subsequent hyperglycemia. Therapeutic approaches for diabetes have focused on compensation of insulin deficiency. The risk of developing cardiovascular diseases is enhanced by diabetes and obesity, predisposing the diabetics to an increase in the incidence and severity of myocardial infarction and heart failure. Although coronary factors explain this enhanced risk in diabetes and obesity, non-coronary factors, such as disturbances in the cardiac oxytocin (OT) system and in the mitochondrial metabolism of glucose in cardiomyocytes (CM) are also implicated in the pathogenesis of left ventricular dysfunction and ischemic injury in the diabetic heart. OT is the most abundant hormone in human body traditionally associated with reproductive functions, acting via specific receptor (OTR). OT has emerged as a pleiotropic hormone with cardiovascular and metabolic functions that mimics insulin actions such as stimulating glucose uptake in tissues. In cardiac muscle, the protective effects of OT are mediated either directly or via natriuretic peptides (NPs) and nitric oxide (NO). In CM, the OT stimulates AMP-activated protein kinase (AMPK), an important target for type-2 diabetes treatment. Increase in glucose uptake in neonatal and adult CM subjected hypoxia is one of the most important cardiovascular and metabolic activity induced by OT. Reduced glucose uptake and oxidation is linked to impaired ventricular function and increased susceptibility to ischemic damage. Stimulation of OT and NPs represents an attractive and novel approach to understand the basis of cardiovascular dysfunction in diabetes.