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FFAR1  -  free fatty acid receptor 1

Homo sapiens

Synonyms: FFA1R, Free fatty acid receptor 1, G-protein coupled receptor 40, GPCR40, GPR40
 
 
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Disease relevance of FFAR1

 

High impact information on FFAR1

 

Psychiatry related information on FFAR1

  • GPR40 was found in the newborn neurons of the normal and postischemic hippocampi of adult macaque monkeys, while the positive effects of PUFA upon Ca(2+) mobilization and cognitive functions were demonstrated in both GPR40 gene-transfected PC12 cells and human subjects with memory deficits [8].
 

Chemical compound and disease context of FFAR1

 

Biological context of FFAR1

  • Overexpressing in these cells the G protein-coupled receptor GPR40, a fatty acid receptor, amplified oleate-induced proliferation, whereas silencing the GPR40 gene using RNA interference decreased it [1].
  • The results suggest that GPR40 is implicated in the control of breast cancer cell growth by fatty acids and that GPR40 may provide a link between fat and cancer [1].
  • In view of the nature of the activating substances, their physiological role in the body, and the tissue distribution of FFAR we suggest the term "nutrient sensing receptor" for receptors acting at the interface between dietary components and signalling molecules [10].
  • The results suggest that EPA regulates cell proliferation in MCF-7 xenografts via a novel inhibitory G protein-coupled, (n-3) FFA receptor-mediated signal transduction pathway [11].
  • It was found to inhibit phosphatidyl inositol hydrolysis induced by linoleic acid (LA) (100 muM in all experiments) in HEK293 cells transfected with FFA(1)R/GPR40 and in the MIN6 subclone, MIN6c4 [12].
 

Anatomical context of FFAR1

 

Associations of FFAR1 with chemical compounds

  • Furthermore, we show that long-chain FFAs amplify glucose-stimulated insulin secretion from pancreatic beta cells by activating GPR40 [5].
  • In study 3 (heparin infusion), FFA levels rose to 1.17 +/- 0.12 mmol/L due to a 4-fold increase in FFA-R (from 1.18 +/- 0.36 to 6.92 +/- 2.40 mumol/L.min; P < 0.05) [16].
  • 3. GW1100 dose dependently inhibited GPR40-mediated Ca2+ elevations stimulated by GW9508 and linoleic acid (pIC50 values of 5.99+/-0.03 and 5.99+/-0.06, respectively) [15].
  • The potential impact of GPR40 mutations on [(3)H]-myo-inositol turnover was estimated in COS-7 cells after stimulation with various concentrations of 5,8,11-eicosatriynoic acid [17].
 

Regulatory relationships of FFAR1

 

Other interactions of FFAR1

  • 7. G protein coupling of GPR40 was examined in Chinese hamster ovary cells expressing the G alpha(q/i)-responsive Gal4-Elk1 reporter system [18].
  • Since agonists of GPR40 are medium to longchain fatty acids and those for GPR41 and 43 are short-chain fatty acids, the family clearly provides an intriguing example of how the ligand specificity, patterns of expression, and function of GPCRs can diverge through evolution [19].
  • The present study was performed to investigate the effects of the GPR40 gene Arg211His polymorphism on clinical and metabolic parameters, including serum insulin level, in 327 healthy Japanese men, using the TaqMan polymerase chain reaction method [20].
 

Analytical, diagnostic and therapeutic context of FFAR1

References

  1. Oleate promotes the proliferation of breast cancer cells via the G protein-coupled receptor GPR40. Hardy, S., St-Onge, G.G., Joly, E., Langelier, Y., Prentki, M. J. Biol. Chem. (2005) [Pubmed]
  2. GPR40 gene expression in human pancreas and insulinoma. Tomita, T., Masuzaki, H., Noguchi, M., Iwakura, H., Fujikura, J., Tanaka, T., Ebihara, K., Kawamura, J., Komoto, I., Kawaguchi, Y., Fujimoto, K., Doi, R., Shimada, Y., Hosoda, K., Imamura, M., Nakao, K. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  3. The G-protein-coupled receptor 40 family (GPR40-GPR43) and its role in nutrient sensing. Covington, D.K., Briscoe, C.A., Brown, A.J., Jayawickreme, C.K. Biochem. Soc. Trans. (2006) [Pubmed]
  4. GPR40 is expressed in glucagon producing cells and affects glucagon secretion. Flodgren, E., Olde, B., Meidute-Abaraviciene, S., Winzell, M.S., Ahrén, B., Salehi, A. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  5. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Itoh, Y., Kawamata, Y., Harada, M., Kobayashi, M., Fujii, R., Fukusumi, S., Ogi, K., Hosoya, M., Tanaka, Y., Uejima, H., Tanaka, H., Maruyama, M., Satoh, R., Okubo, S., Kizawa, H., Komatsu, H., Matsumura, F., Noguchi, Y., Shinohara, T., Hinuma, S., Fujisawa, Y., Fujino, M. Nature (2003) [Pubmed]
  6. GPR40 Is Necessary but Not Sufficient for Fatty Acid Stimulation of Insulin Secretion In Vivo. Latour, M.G., Alquier, T., Oseid, E., Tremblay, C., Jetton, T.L., Luo, J., Lin, D.C., Poitout, V. Diabetes (2007) [Pubmed]
  7. Fatty Acid Signaling in the {beta}-Cell and Insulin Secretion. Nolan, C.J., Madiraju, M.S., Delghingaro-Augusto, V., Peyot, M.L., Prentki, M. Diabetes (2006) [Pubmed]
  8. A putative link of PUFA, GPR40 and adult-born hippocampal neurons for memory. Yamashima, T. Prog. Neurobiol. (2008) [Pubmed]
  9. Existence of GPR40 functioning in a human breast cancer cell line, MCF-7. Yonezawa, T., Katoh, K., Obara, Y. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  10. A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs. Kotarsky, K., Nilsson, N.E., Flodgren, E., Owman, C., Olde, B. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  11. Eicosapentaenoic acid suppresses cell proliferation in MCF-7 human breast cancer xenografts in nude rats via a pertussis toxin-sensitive signal transduction pathway. Sauer, L.A., Dauchy, R.T., Blask, D.E., Krause, J.A., Davidson, L.K., Dauchy, E.M. J. Nutr. (2005) [Pubmed]
  12. Free fatty acid receptor 1 (FFA(1)R/GPR40) and its involvement in fatty-acid-stimulated insulin secretion. Salehi, A., Flodgren, E., Nilsson, N.E., Jimenez-Feltstrom, J., Miyazaki, J., Owman, C., Olde, B. Cell Tissue Res. (2005) [Pubmed]
  13. Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids. Nilsson, N.E., Kotarsky, K., Owman, C., Olde, B. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  14. Uncovering the Pharmacology of the G Protein-Coupled Receptor GPR40: High Apparent Constitutive Activity in Guanosine 5'-O-(3-[35S]thio)triphosphate Binding Studies Reflects Binding of an Endogenous Agonist. Stoddart, L.A., Brown, A.J., Milligan, G. Mol. Pharmacol. (2007) [Pubmed]
  15. Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small molecules. Briscoe, C.P., Peat, A.J., McKeown, S.C., Corbett, D.F., Goetz, A.S., Littleton, T.R., McCoy, D.C., Kenakin, T.P., Andrews, J.L., Ammala, C., Fornwald, J.A., Ignar, D.M., Jenkinson, S. Br. J. Pharmacol. (2006) [Pubmed]
  16. Role of insulin and free fatty acid (FFA) availability on regional FFA kinetics in the human forearm. Capaldo, B., Napoli, R., Di Marino, L., Guida, R., Pardo, F., Saccá, L. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
  17. Studies of relationships between variation of the human G protein-coupled receptor 40 Gene and Type 2 diabetes and insulin release. Hamid, Y.H., Vissing, H., Holst, B., Urhammer, S.A., Pyke, C., Hansen, S.K., Glümer, C., Borch-Johnsen, K., Jørgensen, T., Schwartz, T.W., Pedersen, O., Hansen, T. Diabet. Med. (2005) [Pubmed]
  18. The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids. Briscoe, C.P., Tadayyon, M., Andrews, J.L., Benson, W.G., Chambers, J.K., Eilert, M.M., Ellis, C., Elshourbagy, N.A., Goetz, A.S., Minnick, D.T., Murdock, P.R., Sauls, H.R., Shabon, U., Spinage, L.D., Strum, J.C., Szekeres, P.G., Tan, K.B., Way, J.M., Ignar, D.M., Wilson, S., Muir, A.I. J. Biol. Chem. (2003) [Pubmed]
  19. A family of fatty acid binding receptors. Brown, A.J., Jupe, S., Briscoe, C.P. DNA Cell Biol. (2005) [Pubmed]
  20. GPR40 gene Arg211His polymorphism may contribute to the variation of insulin secretory capacity in Japanese men. Ogawa, T., Hirose, H., Miyashita, K., Saito, I., Saruta, T. Metab. Clin. Exp. (2005) [Pubmed]
  21. Expression of the gene for a membrane-bound fatty acid receptor in the pancreas and islet cell tumours in humans: evidence for GPR40 expression in pancreatic beta cells and implications for insulin secretion. Tomita, T., Masuzaki, H., Iwakura, H., Fujikura, J., Noguchi, M., Tanaka, T., Ebihara, K., Kawamura, J., Komoto, I., Kawaguchi, Y., Fujimoto, K., Doi, R., Shimada, Y., Hosoda, K., Imamura, M., Nakao, K. Diabetologia (2006) [Pubmed]
  22. Free fatty acids increase cytosolic free calcium and stimulate insulin secretion from beta-cells through activation of GPR40. Schnell, S., Schaefer, M., Sch??fl, C. Mol. Cell. Endocrinol. (2007) [Pubmed]
 
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