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Free fatty acid receptor 1: a ray of hope in the therapy of type 2 diabetes mellitus

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Abstract

Free fatty acid receptor 1 (FFAR1) is a G-protein coupled receptor with prominent expression on pancreatic beta cells, bones, intestinal cells as well as the nerve cells. This receptor mediates a multitude of functions in the body including release of incretins, secretion of insulin as well as sensation of pain. Since FFAR1 causes secretion of insulin and regulates glucose metabolism, efforts were made to unfold its structure followed by discovering agonists for the receptor and the utilization of these agonists in the therapy of type 2 diabetes mellitus. Development of such functional FFAR1 agonists is a necessity because the currently available therapy for type 2 diabetes mellitus has numerous drawbacks, of which, the major one is hypoglycemia. Since the most prominent effect of the FFAR1 agonists is on glucose concentration in the body, so the major research is focused on treating type 2 diabetes mellitus, though the agonists could benefit other metabolic disorders and neurological disorders as well. The agonists developed so far had one major limitation, i.e., hepatotoxicity. Although, the only agonist that could reach phase 3 clinical trials was TAK-875 developed by Takeda Pharmaceuticals but it was also withdrawn due to toxic effects on the liver. Thus, there are numerous agonists for the varied binding sites of the receptor but no drug available yet. There does seem to be a ray of hope in the drugs that target FFAR1 but a lot more efforts towards drug discovery would result in the successful management of type 2 diabetes mellitus.

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Author notes

  1. Arpita Arora and Tapan Behl with equal contributions.

Authors and Affiliations

  1. Chitkara College of Pharmacy, Chitkara University, Punjab, India

    Arpita Arora, Tapan Behl, Aayush Sehgal, Sukhbir Singh, Neelam Sharma & Rajwinder Kaur

  2. Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraidah, Kingdom of Saudi Arabia

    Sridevi Chigurupati

  3. Natural and Medical Sciences Research Centre, University of Nizwa, Nizwa, Oman

    Saurabh Bhatia & Ahmed Al-Harrasi

  4. School of Health Science, University of Petroleum and Energy Studies, Dehradun, Uttarakhand, India

    Saurabh Bhatia

  5. Faculty of Pharmacy and Biochemistry, Academic Department of Pharmacology, Bromatology and Toxicology, Centro Latinoamericano de Ensenanza e Investigacion en Bacteriologia Alimentaria, Universidad Nacional Mayor de San Marcos, Lima, Peru

    Celia Vargas-De-La-Cruz

  6. E-Health Research Center, Universidad de Ciencias y Humanidades, Lima, Peru

    Celia Vargas-De-La-Cruz

  7. Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania

    Simona Bungau

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  1. Arpita Arora
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Contributions

AA and TB: conceived the study and wrote the article; AS, SS, NS, and RK: chemical structure work; SC and CVDLC: editing; SB and AAH: data literature; SBU: proof read.

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Correspondence to Tapan Behl.

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Arora, A., Behl, T., Sehgal, A. et al. Free fatty acid receptor 1: a ray of hope in the therapy of type 2 diabetes mellitus. Inflammopharmacol 29, 1625–1639 (2021). https://doi.org/10.1007/s10787-021-00879-8

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