Journal
CELLULAR SIGNALLING
Volume 18, Issue 9, Pages 1360-1365Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2006.03.011
Keywords
free fatty acid; G protein-coupled receptor; glucose homeostasis; diabetes; pancreatic beta-cells; glucagon-like peptide-1
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Free fatty acids (FFAs) are not only an important direct source of energy but they also play key roles in regulating a range of physiological responses. Although it was long assumed that such effects of FFAs must occur following cellular uptake, and potentially via their conversion to fatty acyl-CoAs, it is now apparent that FFAs also function directly as agonists at a number of G protein-coupled receptors (GPCRs). Tissue distribution studies and, subsequently, siRNA knock-down experiments have indicated key roles for these GPCRs in glucose homeostasis, adipogenesis, white cell recruitment and potentially in a range of other processes. Considerable interest is thus now centred on the generation of potent and selective small molecule ligands, both as tool compounds to further unravel the biology and physiological role of this group of GPCRs and as starting points for possible therapeutic intervention in a range of areas, particularly those associated with 'metabolic syndrome'. (c) 2006 Elsevier Inc. All rights reserved.
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