Involvement of the pancreatic renin-angiotensin system in insulin resistance and the metabolic syndrome.
The cardiometabolic syndrome consists of several major components: hypertension, hyperinsulinemia, hyperlipidemia, and hyperglycemia. Central to this syndrome are insulin resistance and generation of reactive oxygen species; these features are particularly prominent in patients with type 2 diabetes mellitus. In this context, large clinical trials have shown that blockade of the renin-angiotensin system (RAS) is protective against type 2 diabetes. In spite of these solid clinical data, the mechanistic pathways by which RAS blockade achieves these protective effects have yet to be resolved. A recently identified local pancreatic islet RAS has, however, been implicated in this regard. Furthermore, RAS blockade was recently shown to enhance islet blood flow, oxygen tension, and insulin biosynthesis, thus improving beta-cell function and glucose tolerance. Meanwhile, RAS activation may also influence islet cell inflammatory responses, apoptosis, fibrosis, and superoxide anion production. This RAS-associated oxidative stress can induce islet cell dysfunction in the pancreas and insulin resistance in peripheral tissues.
Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China. psleung@cuhk.edu.hk
Po Sing
PS
Leung
Marc
M
de Gasparo
D017667:Adipocytes / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D042783:Endothelial Cells / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D017382:Reactive Oxygen Species; D005947:Glucose