The renin–angiotensin–aldosterone system and glucose homeostasis

• Published in: Trends in pharmacological sciences (Regular ed.) 2011-12, Vol.32 (12), p.734-739
• Main Authors: Luther, James Matthew, Brown, Nancy J
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Animals; Diabetes Mellitus - etiology; Diabetes Mellitus - metabolism; Diabetes Mellitus - prevention & control; Glucose Metabolism Disorders - etiology; Glucose Metabolism Disorders - metabolism; Glucose Metabolism Disorders - prevention & control; Humans; Insulin Resistance; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Molecular Targeted Therapy; Obesity - drug therapy; Obesity - metabolism; Obesity - physiopathology; Renin-Angiotensin System - drug effects
• ISSN: 0165-6147; 1873-3735
• DOI: 10.1016/j.tips.2011.07.006

The renin–angiotensin–aldosterone system (RAAS) is inappropriately activated in obesity. In individuals at risk for diabetes, RAAS inhibition protects against kidney and heart disease, and also reduces the incidence of diabetes in large clinical trials. At a cellular level, angiotensin II (Ang II) and aldosterone induce insulin resistance by increasing oxidative stress and altering insulin signaling, leading to decreased glucose transport. Ang II also contributes to oxidative stress, inflammation, and apoptosis in pancreatic β cells. Aldosterone diminishes glucose-stimulated insulin secretion in vivo and in vitro from isolated pancreatic islets and cultured β cells through a mineralocorticoid receptor (MR)-independent mechanism. We review these findings in the context of pharmacological strategies interrupting the RAAS to highlight the potential application of these strategies to the prevention of diabetes progression.