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Type: Journal article
Title: Free fatty acid receptors: emerging targets for treatment of diabetes and its complications
Author: Vangaveti, V.
Shashidhar, V.
Jarrod, G.
Baune, B.
Kennedy, R.
Citation: Therepeutic Advances in Endocrinology and Metabolic Disorders, 2010; 1(4):165-175
Publisher: Sage Publications Ltd
Issue Date: 2010
ISSN: 2042-0188
Statement of
Venkat Vangaveti, Venkatesh Shashidhar, Ghassan Jarrod, Bernhard T. Baune and R. Lee Kennedy
Abstract: Fatty acids (FAs) are important as metabolic substrates and as structural components of biological membranes. However, they also function as signalling molecules. Recently, a series of G protein-coupled receptors (GPRs) for FAs has been described and characterized. These receptors have differing specificities for FAs of differing chain length and degree of saturation, for FA derivatives such as oleoylethanolamide, and for oxidized FAs. They are a critical component of the body’s nutrient sensing apparatus, and small molecule agonists and antagonists of these receptors show considerable promise in the management of diabetes and its complications. Agonists of the long-chain free fatty acid receptors FFAR1 and GPR119 act as insulin secretagogues, both directly and by increasing incretins. Although, drugs acting at short-chain FFA receptors (FFAR2 and FFAR3) have not yet been developed, they are attractive targets as they regulate nutrient balance through effects in the intestine and adipose tissue. These include regulation of the secretion of cholecystokinin, peptide YY and leptin. Finally, GPR132 is a receptor for oxidized FAs, which may be a sensor of lipid overload and oxidative stress, and which is involved in atherosclerosis. Regulation of its signalling pathways with drugs may decrease the macrovascular risk experienced by diabetic patients. In summary, FA receptors are emerging drug targets that are involved in the regulation of nutrient status and carbohydrate tolerance, and modulators of these receptors may well figure prominently in the next generation of antidiabetic drugs.
Keywords: atherosclerosis; diabetes; drug therapies; free fatty acid; G protein-coupled receptor
Rights: © The Author(s), 2010.
RMID: 0020111226
DOI: 10.1177/2042018810381066
Appears in Collections:Psychiatry publications

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