期刊
FRONTIERS IN ENDOCRINOLOGY
卷 5, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fendo.2014.00137
关键词
diabetes; FFA receptor; insulin; incretin; inflammation
资金
- Biotechnology and Biosciences Research Council [BB/K019864/1]
- Canadian Institutes of Health Research
- Danish Council for Strategic Research [11-116196]
- BBSRC [BB/K019864/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/K019864/1] Funding Source: researchfish
Dietary free fatty acids (FFAs), such as omega-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 glycemic 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 programs within industry and academia aimed at improving the safety and effectiveness of these potential treatments.
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