Treatment of type 2 diabetes by free fatty acid receptor agonists

Watterson, K. R., Hudson, B. D. , Ulven, T. and Milligan, G. (2014) Treatment of type 2 diabetes by free fatty acid receptor agonists. Frontiers in Endocrinology, 5, 137. (doi: 10.3389/fendo.2014.00137) (PMID:25221541) (PMCID:PMC4147718)

Abstract

Dietary free fatty acids (FFAs), such as ω-3 fatty acids, regulate metabolic and anti-inflammatory processes, with many of these effects attributed to FFAs interacting with a family of G protein-coupled receptors. Selective synthetic ligands for Free Fatty Acid receptors (FFA1-4) have consequently been developed as potential treatments for type 2 diabetes (T2D). In particular, clinical studies show that Fasiglifam, an agonist of the long chain FFA receptor, FFA1, improved glycaemic control and reduced HbA1c levels in T2D patients, with a reduced risk of hypoglycemia. However, this ligand was removed from clinical trials due to potential liver toxicity and determining if this is a target or a ligand-specific feature is now of major importance. Pre-clinical studies also show that FFA4 agonism increases insulin sensitivity, induces weight loss and reduces inflammation and the metabolic and anti-inflammatory effects of short chain fatty acids (SCFAs) are linked with FFA2 and FFA3 activation. In this review, we therefore show that FFA receptor agonism is a potential clinical target for T2D treatment and discuss ongoing drug development programmes within industry and academia aimed at improving the safety and effectiveness of these potential treatments.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Watterson, Dr Kenneth and Hudson, Dr Brian and Milligan, Professor Graeme
• Authors: Watterson, K. R., Hudson, B. D., Ulven, T., and Milligan, G.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Frontiers in Endocrinology
• Publisher: Frontiers Research Foundation
• ISSN: 1664-2392
• ISSN (Online): 1664-2392
• Copyright Holders: Copyright © 2014 The Authors
• First Published: First published in Frontiers in Endocrinology 5:137
• Publisher Policy: Reproduced under a Creative Commons License