Circulation research
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Circulation research · Feb 2008
ReviewPeroxisome proliferator-activated receptor-gamma-mediated effects in the vasculature.
Peroxisome proliferator-activated receptor (PPAR)-gamma is a nuclear receptor and transcription factor in the steroid superfamily. PPAR-gamma agonists, the thiazolidinediones, are clinically used to treat type 2 diabetes. In addition to its function in adipogenesis and increasing insulin sensitivity, PPAR-gamma also plays critical roles in the vasculature. ⋯ Both human genetic studies and animal studies using transgenic mice have demonstrated the importance of PPAR-gamma in these disorders. However, recent clinical studies have raised significant concerns about the cardiovascular side effects of thiazolidinediones, particularly rosiglitazone. Weighing the potential benefit and harm of PPAR-gamma activation and exploring the functional mechanisms may provide a balanced view on the clinical use of these compounds and new approaches to the future therapeutics of vascular disorders associated with diabetes.
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Circulation research · Feb 2008
ReviewThe sulfonylurea receptor, an atypical ATP-binding cassette protein, and its regulation of the KATP channel.
ATP-binding cassette (ABC) proteins are highly conserved and widely expressed throughout nature and found in all organisms, both prokaryotic and eukaryotic. They mediate myriad critical cellular processes, from nutrient import to toxin efflux using the energy derived from ATP hydrolysis. Most ABC proteins mediate transport of substances across lipid membranes. ⋯ K(ATP) is particularly important in the regulation of insulin secretion from pancreatic beta-cells and in regulating action potential duration in muscle cells. SUR is indispensable for normal channel function, and mutations in genes encoding SURs increase the susceptibility to diabetes, myocardial infarction, and heart failure. Here, we review the structure and function of ABC proteins and discuss SUR, its regulation of the K(ATP) channel, and its role in cardiovascular disease.