Role of the renin-angiotensin- aldosterone system in the metabolic syndrome.
Clinical trials of angiotensin-converting enzyme inhibitors and angiotensin type 1- receptor blockers have demonstrated a significant reduction in cardiovascular, renal and new-onset diabetes risk. This finding raises the question on the pathophysiological role of the renin-angiotensin-aldosterone system (RAAS) in the Metabolic Syndrome. Inappropriate activation of the RAAS in the circulation but also on the tissue level, suggests profound changes in the regulation of this system in the Metabolic Syndrome. Possible physiological and molecular mechanisms that link the RAAS with the Metabolic Syndrome include interactions between insulin and angiotensin type 1-receptors, hemodynamic effects that change nutrient partition to tissues such as skeletal muscle and adipose tissue, inhibition of adipogenesis which may limit the storage capacity of adipose tissue and allows ectopic lipid storage which leads to lipotoxicity, influence on adipokine secretion, and influence on insulin secretion from pancreatic Beta-cells. Most of these mechanisms are linked with decreased insulin sensitivity. Convincing experimental evidence on these possible mechanisms, however, is rare, and several obscurities remain, which are partly due to species differences between rodent models and humans. Thus, data from clinical trials clearly suggest that the RAAS plays an important role for the pathophysiology of the Metabolic Syndrome, but the molecular mechanisms are not understood very well at present.
Engeli
Stefan
S
Franz Volhard Clinical Research Center, Charité Campus Buch, Berlin, Germany.
D000818:Animals; D006801:Humans; D024821:Metabolic Syndrome / Q000378:metabolism / Q000503:physiopathology*; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D012084:Renin-Angiotensin System / Q000502:physiology*