Of the renin-angiotensin system and reactive oxygen species: Type 2 diabetes and angiotensin II inhibition

摘要: Rates of type 2 diabetes mellitus are increasing worldwide at an explosive rate. This “epidemic” is largely driven by a concomitant obesity epidemic, which seen not only in affluent countries, but industrializing countries as well, with the rapid change toward Western life-style patterns worldwide. Recent clinical trials such Heart Outcomes Prevention Evaluation (HOPE), Losartan Intervention for Endpoint reduction (LIFE), and Study Cognition Prognosis Elderly (SCOPE) have indicated that blocking renin-angiotensin system (RAS) may reduce risk developing mellitus. effect be explained variety diabetogenic factors, seem to moderated angiotensin II, free fatty acids (FFA) phenomena adipocyte differentiation, well inflammation oxidative damage. Insulin resistance, usually present cases impaired glucose tolerance, major identifiable defect subjects diabetes. Elevated FFA levels result reduced activation phosphoinositol-3 kinase, enzyme essential normal insulin-stimulated uptake. potentiated II consequently uptake improved RAS inhibition. Furthermore, blockade AT 1 -receptor has been shown stimulate differentiation adipocytes store FFAs, leads plasma decreased insulin resistance. There also data suggesting reduces inflammatory production reactive oxygen species (ROS), factor pathophysiology cardiovascular factor. Both proinflammatory molecules ROS increase resistance atherogenesis. It thought FFAs hyperglycemia stress, leading signaling nuclear κ-B other mediators stress-sensitive pathways, increases will lead β-cell dysfunction diabetic complications during longer term. Inhibiting seems on several steps this cascade. obvious need large-scale specifically designed assess protective benefits individuals Two prevention ongoing, Diabetes Reduction Assessment Ramipril Rosiglitazone Medications (DREAM) study more ambitious Nateglinide Valsartan Impaired Glucose Tolerance Research (NAVIGATOR) trial, assessing events.