Chapter title |
The Role and Future of FFA1 as a Therapeutic Target
|
---|---|
Chapter number | 51 |
Book title |
Free Fatty Acid Receptors
|
Published in |
Handbook of experimental pharmacology, November 2016
|
DOI | 10.1007/164_2016_51 |
Pubmed ID | |
Book ISBNs |
978-3-31-950692-0, 978-3-31-950693-7
|
Authors |
Julien Ghislain, Vincent Poitout |
Editors |
Graeme Milligan, Ikuo Kimura |
Abstract |
Of the 415 million people suffering from diabetes worldwide, 90% have type 2 diabetes. Type 2 diabetes is characterized by hyperglycemia and occurs in obese individuals as a result of insulin resistance and inadequate insulin levels. Accordingly, diabetes drugs are tailored to enhance glucose disposal or target the pancreatic islet β cell to increase insulin secretion. The majority of the present-day insulin secretagogues, however, increase the risk of iatrogenic hypoglycemia, and hence alternatives are actively sought. The long-chain fatty acid, G protein-coupled receptor FFA1/Gpr40, is expressed in β cells, and its activation potentiates insulin secretion in a glucose-dependent manner. Preclinical data indicate that FFA1 agonism is an effective treatment to restore glucose homeostasis in rodent models of diabetes. This initial success prompted clinical trials in type 2 diabetes patients, the results of which were promising; however, the field suffered a significant setback when the lead compound TAK-875/fasiglifam was withdrawn from clinical development due to liver safety concerns. Nevertheless, recent developments have brought to light a surprising complexity of FFA1 agonist action, signaling diversity, and biological outcomes, raising hopes that with a greater understanding of the mechanisms at play the second round will be more successful. |
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Demographic breakdown
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Researcher | 4 | 12% |
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Other | 2 | 6% |
Unknown | 14 | 41% |
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