Drug discovery opportunities and challenges at G protein coupled receptors for long chain free fatty acids

Frontiers in Endocrinology

Volumn 3, Issue JAN, 2012, Pages

  Holliday, Nicholas D ^a   Watson, Sarah Jane ^a   Brown, Alastair J H ^b  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^b ASTRAZENECA   (United Kingdom)

Author keywords

Adipocytes; FFA1; Free fatty acid; G protein coupled receptor; GPR120; GPR40; Pancreas; Type 2 diabetes

Indexed keywords

EID: 84874393546     PISSN: None     EISSN: 16642392     Source Type: Journal    
DOI: 10.3389/fendo.2011.00112     Document Type: Review

References (91)

1. Alquier, T., Peyot, M. L., Latour, M. G., Kebede, M., Sorensen, C. M., Gesta, S., Ronald Kahn, C., Smith, R. D., Jetton, T. L., Metz, T. O., Prentki, M., and Poitout, V. (2009). Deletion of GPR40 impairs glucose-induced insulin secretion in vivo in mice without affecting intracellular fuel metabolism in islets. Diabetes 58, 2607-2615.
2. Arakawa, K., Nishimura, T., Sugimoto, Y., Takahashi, H., and Shimamura, T. (2010). Novel isoindolin-1-one derivative. International Patent WO 2010/104195.
3. Bartoschek, S., Klabunde, T., Defossa, E., Dietrich, V., Stengelin, S., Griesinger, C., Carlomagno, T., Focken, I., and Wendt, K. U. (2010). Drug design for G-protein-coupled receptors by a ligand-based NMR method. Angew. Chem. Int. Ed. Engl. 49, 1426-1429.
4. Boden, G., and Shulman, G. I. (2002). Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and b-cell dysfunction. Eur. J. Clin. Invest. 32(Suppl. 3), 14-23.
5. 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., and Jenkinson, S. (2006). Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small molecules. Br. J. Pharmacol. 148, 619-628.
6. 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. Jr., Shabon, U., Spinage, L. D., Strum, J. C., Szekeres, P. G., Tan, K. B., Way, J. M., Ignar, D. M., Wilson, S., and Muir, A. I. (2003). The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids. J. Biol. Chem. 278, 11303-11311.
7. Brown, S. P., Dransfield, P. J., Heuze, J., Kohn, T. J., Liu, J., Medina, J., Pateropomg, V., Shen, W., Vimolratana, M., Wang, Y., Lu, M., and Zhu, L. (2010). Conformationally constrained carboxylic acid derivatives useful for treating metabolic disorders. US Patent 2010/0298367A1.
8. Burns, R. N., and Moniri, N. H. (2010). Agonism with the omega-3 fatty acids alpha-linolenic acid and docosahexaenoic acid mediates phosphorylation of both the short and long isoforms of the human GPR120 receptor. Biochem. Biophys. Res. Commun. 396, 1030-1035.
9. Calder, P. C. (2008). The relationship between the fatty acid composition of immune cells and their function. Prostaglandins Leukot. Essent. Fatty Acids 79, 101-108
10. Cartoni, C., Yasumatsu, K., Ohkuri, T., Shigemura, N.,Yoshida, R., Godinot, N., Le Coutre, J., Ninomiya, Y., and Damak, S. (2010). Taste preference for fatty acids is mediated by GPR40 and GPR120. J. Neurosci. 30, 8376-8382.
11. Christiansen, E., Urban, C., Grundmann, M., Due-Hansen, M. E., Hagesaether, E., Schmidt, J., Pardo, L., Ullrich, S., Kostenis, E., Kassack, M. U., and Ulven, T. (2011). Identification of a potent and selective free fatty acid receptor 1 (FFA1/GPR40) agonist with favorable physicochemical and in vitro ADME properties. J. Med. Chem. 54, 6691-6703.
12. Christiansen, E., Urban, C., Merten, N., Liebscher, K., Karlsen, K. K., Hamacher, A., Spinrath, A., Bond, A. D., Drewke, C., Ullrich, S., Kassack, M. U., Kostenis, E., and Ulven, T. (2008). Discovery of potent and selective agonists for the free fatty acid receptor 1 (FFA(1)/GPR40), a potential target for the treatment of type II diabetes. J. Med. Chem. 51, 7061-7064.
13. Cornish, J., MacGibbon, A., Lin, J. M., Watson, M., Callon, K. E., Tong, P. C., Dunford, J. E., van der Does, Y., Williams, G. A., Grey, A. B., Naot, D., and Reid, I. R. (2008). Modulation of osteoclastogenesis by fatty acids. Endocrinology 149, 5688-5695.
14. Delhanty, P. J., van Kerkwijk, A., Huisman, M., van de Zande, B., Verhoef-Post, M., Gauna, C., Hofland, L., Themmen, A. P., and van der Lely, A. J. (2010). Unsaturated fatty acids prevent desensitization of the human growth hormone secretagogue receptor by blocking its internalization. Am. J. Physiol. Endocrinol. Metab. 299, E497-E505.
15. Dhayal, S., Welters, H. J., and Morgan, N. G. (2008). Structural requirements for the cytoprotective actions of mono-unsaturated fatty acids in the pancreatic beta-cell line, BRIN-BD11. Br. J. Pharmacol. 153, 1718-1727.
16. Dramane, G., Akpona, S., Simonin, A. M., Besnard, P., and Khan, N. A. (2011). Cell signaling mechanisms of gustatory perception of lipids: can the taste cells be the target of antiobesity agents? Curr. Med. Chem. 18, 3417-3422.
17. Edfalk, S., Steneberg, P., and Edlund, H. (2008). Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion. Diabetes 57, 2280-2287.
18. Fang, Y., Ferrie, A. M., Fontaine, N. H., Mauro, J., and Balakrishnan, J. (2006). Resonant waveguide grating biosensor for living cell sensing. Biophys. J. 91, 1925-1940.
19. Flodgren, E., Olde, B., Meidute-Abaraviciene, S., Winzell, M. S., Ahren, B., and Salehi, A. (2007). GPR40 is expressed in glucagon producing cells and affects glucagon secretion. Biochem. Biophys. Res. Commun. 354, 240-245.
20. Fredriksson, R., Hoglund, P. J., Gloriam, D. E., Lagerstrom, M. C., and Schioth, H. B. (2003). Seven evolutionarily conserved human rhodopsin G protein-coupled receptors lacking close relatives. FEBS Lett. 554, 381-388.
21. Gardner, O. S., Dewar, B. J., and Graves, L. M. (2005). Activation of mitogenactivated protein kinases by peroxisome proliferator-activated receptor ligands: an example of nongenomic signaling. Mol. Pharmacol. 68, 933-941.
22. Garrido, D. M., Corbett, D. F., Dwornik, K. A., Goetz, A. S., Littleton, T. R., Mckeown, S. C., Mills, W. Y., Smalley, T. L. Jr., Briscoe, C. P., and Peat, A. J. (2006). Synthesis and activity of small molecule GPR40 agonists. Bioorg. Med. Chem. Lett. 16, 1840-1845.
23. Gawrisch, K., Soubias, O., and Mihailescu, M. (2008). Insights from biophysical studies on the role of polyunsaturated fatty acids for function of G-protein coupled membrane receptors. Prostaglandins Leukot. Essent. Fatty Acids 79, 131-134.
24. Gotoh, C., Hong, Y. H., Iga, T., Hishikawa, D., Suzuki, Y., Song, S. H., Choi, K. C., Adachi, T., Hirasawa, A., Tsujimoto, G., Sasaki, S., and Roh, S. G. (2007). The regulation of adipogenesis through GPR120. Biochem. Biophys. Res. Commun. 354, 591-597.
25. Hara, T., Hirasawa, A., Sun, Q., Koshimizu, T. A., Itsubo, C., Sadakane, K., Awaji, T., and Tsujimoto, G. (2009a). Flow cytometry-based binding assay for GPR40 (FFAR1; free fatty acid receptor 1). Mol. Pharmacol. 75, 85-91.
26. Hara, T., Hirasawa, A., Sun, Q., Sadakane, K., Itsubo, C., Iga, T., Adachi, T., Koshimizu, T. A., Hashimoto, T., Asakawa,Y., and Tsujimoto, G. (2009b). Novel selective ligands for free fatty acid receptors GPR120 and GPR40. Naunyn Schmiedebergs Arch. Pharmacol. 380, 247-255.
27. Hashimoto, N., Sasaki, Y., Nakama, C., and Ishikawa, M. (2010). Novel phenyl-isoxazol-3-ol derivative. US Patent 2010/0130559.
28. Herling, A. W., Defossa, E., Haschke, G., Dietrich, V., Stengelin, S., Keil, S., Dudda, A., Wagner, M., Ruus, P., and Ruetten, H. (2011). "Pharmacological activation of GPR40 reduces increased blood glucose levels by modulated insulin secretion in a glucose-dependent manner," in 71st American Diabetes Association Meeting (Poster Presentation),SanDiego, CA, 0452-PP.
29. Hirasawa, A., Tsumaya, K., Awaji, T., Katsuma, S., Adachi, T., Yamada, M., Sugimoto, Y., Miyazaki, S., and Tsujimoto, G. (2005). Free fatty acids regulate gut incretin glucagonlike peptide-1 secretion through GPR120. Nat. Med. 11, 90-94.
30. Hu, H., He, L. Y., Gong, Z., Li, N., Lu, Y. N., Zhai, Q. W., Liu, H., Jiang, H. L., Zhu, W. L., and Wang, H. Y. (2009). A novel class of antagonists for the FFAs receptor GPR40. Biochem. Biophys. Res. Commun. 390, 557-563.
31. Hudson, B. D., Smith, N., and Milligan, G. (2011). Experimental challenges to targeting poorly characterized GPCRs: uncovering the therapeutic potential for free fatty acid receptors Adv. Pharmacol. 62, 175-218.
32. Humphries, P. S., Benbow, J. W., Bonin, P. D., Boyer, D., Doran, S. D., Frisbie, R. K., Piotrowski, D. W., Balan, G., Bechle, B. M., Conn, E. L., Dirico, K. J., Oliver, R. M., Soeller, W. C., Southers, J. A., and Yang, X. (2009). Synthesis and SAR of 1,2,3,4-tetrahydroisoquinolin1-ones as novel G-protein-coupled receptor 40 (GPR40) antagonists. Bioorg. Med. Chem. Lett. 19, 2400-2403.
33. Ichimura, A., Hirasawa, A., Hara, T., and Tsujimoto, G. (2009). Free fatty acid receptors act as nutrient sensors to regulate energy homeostasis. Prostaglandins Other Lipid Mediat. 89, 82-88.
34. 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., and Fujino, M. (2003). Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature 422, 173-176
35. Jagannath, M. M., Somesh, B. P., Venkataranganna, M. R., Anup, O., Anilkumar, D., Verma, M. K., Sanghamitra, B., Bhawna, C., Manojkumar, S., Sowmya, R., Jayalakshmi, S., and Sunil, V. (2011). "CNX-011-67, a novel orally available GPR40 agonist, enhances glucose stimulated insulin secretion and significantly reduces fasting and non-fasting hyperglycemia - studies in vitro and in vivo in a preclinical model of type 2 diabetes," in 71st American Diabetes Association Meeting (Poster Presentation),SanDiego, CA, 0031-LB.
36. Katsuma, S., Hatae, N., Yano, T., Ruike, Y., Kimura, M., Hirasawa, A., and Tsujimoto, G. (2005). Free fatty acids inhibit serum deprivationinduced apoptosis through GPR120 in a murine enteroendocrine cell line STC-1. J. Biol. Chem. 280, 19507-19515.
37. Kebede, M., Alquier, T., Latour, M. G., Semache, M., Tremblay, C., and Poitout, V. (2008). The fatty acid receptor GPR40 plays a role in insulin secretion in vivo after high-fat feeding. Diabetes 57, 2432-2437.
38. Kilpatrick, L. E., Briddon, S. J., Hill, S. J., and Holliday, N. D. (2010). Quantitative analysis of neuropeptideY receptor association with betaarrestin2 measured by bimolecular fluorescence complementation. Br. J. Pharmacol. 160, 892-906.
39. Kobilka, B. K. (2011). Structural insights into adrenergic receptor function and pharmacology. Trends Pharmacol. Sci. 32, 213-218.
40. Kotarsky, K., Nilsson, N. E., Flodgren, E., Owman, C., and Olde, B. (2003). A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs. Biochem. Biophys. Res. Commun. 301, 406-410.
41. Lan, H., Hoos, L. M., Liu, L., Tetzloff, G., Hu, W., Abbondanzo, S. J., Vassileva, G., Gustafson, E. L., Hedrick, J. A., and Davis, H. R. (2008). Lack of FFAR1/GPR40 does not protect mice from high-fat dietinduced metabolic disease. Diabetes 57, 2999-3006.
42. Latour, M. G., Alquier, T., Oseid, E., Tremblay, C., Jetton, T. L., Luo, J., Lin, D. C., and Poitout, V. (2007). GPR40 is necessary but not sufficient for fatty acid stimulation of insulin secretion in vivo. Diabetes 56, 1087-1094.
43. Lee, T., Schwandner, R., Swaminath, G., Weiszmann, J., Cardozo, M., Greenberg, J., Jaeckel, P., Ge, H., Wang, Y., Jiao, X., Liu, J., Kayser, F., Tian, H., and Li, Y. (2008). Identification and functional characterization of allosteric agonists for the G protein-coupled receptor FFA2. Mol. Pharmacol. 74, 1599-1609.
44. Liou, A. P., Lu, X., Sei,Y., Zhao, X., Pechhold, S., Carrero, R. J., Raybould, H. E., and Wank, S. (2011). The G-protein-coupled receptor GPR40 directly mediates long-chain fatty acid-induced secretion of cholecystokinin. Gastroenterology 140, 903-912.
45. Ma, D., Tao, B.,Warashina, S., Kotani, S., Lu, L., Kaplamadzhiev, D. B., Mori, Y., Tonchev, A. B., and Yamashima, T. (2007). Expression of free fatty acid receptor GPR40 in the central nervous system of adult monkeys. Neurosci. Res. 58, 394-401.
46. Ma, J., Novack, A., Nashashibi, I., Pham, P., Rabbat, C. J., Song, J., Shi, D. F., Zhao, Z., Choi, Y. J., and Chen, X. (2010). Aryl GPR120 receptor agonists and uses thereof. International Patent WO 2010/048207.
47. Matsumura, S., Eguchi, A., Mizushige, T., Kitabayashi, N., Tsuzuki, S., Inoue, K., and Fushiki, T. (2009). Colocalization of GPR120 with phospholipase-Cbeta2 and alphaustducin in the taste bud cells in mice. Neurosci. Lett. 450, 186-190.
48. May, L. T., Leach, K., Sexton, P. M., and Christopoulos, A. (2007). Allosteric modulation of G protein-coupled receptors. Annu. Rev. Pharmacol. Toxicol. 47, 1-51.
49. Miyauchi, S., Hirasawa, A., Iga, T., Liu, N., Itsubo, C., Sadakane, K., Hara, T., and Tsujimoto, G. (2009). Distribution and regulation of protein expression of the free fatty acid receptor GPR120. Naunyn Schmiedebergs Arch. Pharmacol. 379, 427-434.
50. Moore, K., Zhang, Q., Murgolo, N., Hosted, T., and Duffy, R. (2009). Cloning, expression, and pharmacological characterization of the GPR120 free fatty acid receptor from cynomolgus monkey: comparison with human GPR120 splice variants. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 154, 419-426.
51. Nagasumi, K., Esaki, R., Iwachidow, K., Yasuhara, Y., Ogi, K., Tanaka, H., Nakata, M., Yano, T., Shimakawa, K., Taketomi, S., Takeuchi, K., Odaka, H., and Kaisho, Y. (2009). Overexpression of GPR40 in pancreatic {beta}-cells augments glucose stimulated insulin secretion and improves glucose tolerance in normal and diabetic mice. Diabetes 58, 1067-1076.
52. Naik, H., Vakilynejad, M., Wu, J., Viswanathan, P., Dote, N., Higuchi, T., and Leifke, E. (2011). Safety, tolerability, pharmacokinetics, and pharmacodynamic properties of the GPR40 agonist TAK-875: results from a double-blind, placebo-controlled single oral dose rising study in healthy volunteers. J. Clin. Pharmacol. (in press). doi:10.1177/0091270011409230
53. Negoro, N., Sasaki, S., Mikami, S., Ito, M., Suzuki, M., Tsujihata, Y., Ito, R., Harada, A., Takeuchi, K., Suzuki, N., Miyazaki, J., Santou, T., Odani, T., Kanzaki, N., Funami, M., Tanaka, T., Kogame, A., Matsunaga, S., Yasuma, T., and Momose, Y. (2010). Discovery of TAK-875: a potent, selective, and orally bioavailable GPR40 agonist. ACS Med. Chem. Lett. 1, 290-294.
54. Ogawa, T., Hirose, H., Miyashita, K., Saito, I., and Saruta, T. (2005). GPR40 gene Arg211His polymorphism may contribute to the variation of insulin secretory capacity in Japanese men. Metab. Clin. Exp. 54, 296-299.
55. Ogden, C. L., Carroll, M. D., Curtin, L. R., Mcdowell, M. A., Tabak, C. J., and Flegal, K. M. (2006). Prevalence of overweight and obesity in the United States, 1999-2004. J. Am. Med. Assoc. 295, 1549-1555.
56. Oh, D. Y., Talukdar, S., Bae, E. J., Imamura, T., Morinaga, H., Fan, W., Li, P., Lu, W. J., Watkins, S. M., and Olefsky, J. M. (2010). GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142, 687-698.
57. Overington, J. P., Al-Lazikani, B., and Hopkins, A. L. (2006). How many drug targets are there? Nat. Rev. Drug Discov. 5, 993-996.
58. Pin, J. P., Neubig, R., Bouvier, M., Devi, L., Filizola, M., Javitch, J. A., Lohse, M. J., Milligan, G., Palczewski, K., Parmentier, M., and Spedding, M. (2007). International Union of Basic and Clinical Pharmacology. LXVII. Recommendations for the recognition and nomenclature of G proteincoupled receptor heteromultimers. Pharmacol. Rev. 59, 5-13.
59. Rajagopal, S., Rajagopal, K., and Lefkowitz, R. J. (2010). Teaching old receptors new tricks: biasing seventransmembrane receptors. Nat. Rev. Drug Discov. 9, 373-386.
60. Rennie, K. L., and Jebb, S. A. (2005). Prevalence of obesity in great Britain. Obes. Rev. 6, 11-12.
61. Sasaki, S., Kitamura, S., Negoro, N., Suzuki, M., Tsujihata, Y., Suzuki, N., Santou, T., Kanzaki, N., Harada, M., Tanaka, Y., Kobayashi, M., Tada, N., Funami, M., Tanaka, T., Yamamoto, Y., Fukatsu, K., Yasuma, T., and Momose, Y. (2011). Design, synthesis, and biological activity of potent and orally available G proteincoupled receptor 40 agonists. J. Med. Chem. 54, 1365-1378.
62. Schmidt, J., Liebscher, K., Merten, N., Grundmann, M., Mielenz, M., Sauerwein, H., Christiansen, E., Due-Hansen, M. E., Ulven, T., Ullrich, S., Gomeza, J., Drewke, C., and Kostenis, E. (2011). Conjugated linoleic acids mediate insulin release through islet G proteincoupled receptor FFA1/GPR40. J. Biol. Chem. 286, 11890-11894.
63. Schröder, R., Janssen, N., Schmidt, J., Kebig, A., Merten, N., Hennen, S., Muller, A., Blattermann, S., Mohr-Andra, M., Zahn, S., Wenzel, J., Smith, N. J., Gomeza, J., Drewke, C., Milligan, G., Mohr, K., and Kostenis, E. (2010). Deconvolution of complex G protein-coupled receptor signaling in live cells using dynamic mass redistribution measurements. Nat. Biotechnol. 28, 943-949.
64. Serhan, C. N., Krishnamoorthy, S., Recchiuti, A., and Chiang, N. (2011). Novel anti-inflammatory - proresolving mediators and their receptors. Curr. Top. Med. Chem. 11, 629-647.
65. Smith, N. J., and Milligan, G. (2010). Allostery at G protein-coupled receptor homoand heteromers: uncharted pharmacological landscapes. Pharmacol. Rev. 62, 701-725.
66. Smith, N. J., Stoddart, L. A., Devine, N. M., Jenkins, L., and Milligan, G. (2009). The action and mode of binding of thiazolidinedione ligands at free fatty acid receptor 1. J. Biol. Chem. 284, 17527-17539.
67. Smith, N. J., Ward, R. J., Stoddart, L. A., Hudson, B. D., Kostenis, E., Ulven, T., Morris, J. C., Trankle, C., Tikhonova, I. G., Adams, D. R., and Milligan, G. (2011). Extracellular loop 2 of the free fatty acid receptor 2 mediates allosterism of a phenylacetamide ago-allosteric modulator. Mol. Pharmacol. 80, 163-173.
68. Steneberg, P., Rubins, N., Bartoov-Shifman, R., Walker, M. D., and Edlund, H. (2005). The FFA receptor GPR40 links hyperinsulinemia, hepatic steatosis, and impaired glucose homeostasis in mouse. Cell Metab. 1, 245-258.
69. Stewart, G., Hira, T., Higgins, A., Smith, C. P., and Mclaughlin, J. T. (2006). Mouse GPR40 heterologously expressed in Xenopus oocytes is activated by short-, medium-, and long-chain fatty acids. Am. J. Physiol. Cell Physiol. 290, C785-C792.
70. Stoddart, L. A., Brown, A. J., and Milligan, G. (2007). 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. Mol. Pharmacol. 71, 994-1005.
71. Stoddart, L. A., Smith, N. J., and Milligan, G. (2008). International Union of Pharmacology. LXXI. Free fatty acid receptors FFA1, -2, and -3: pharmacology and pathophysiological functions. Pharmacol. Rev. 60, 405-417.
72. Sum, C. S., Tikhonova, I. G., Neumann, S., Engel, S., Raaka, B. M., Costanzi, S., and Gershengorn, M. C. (2007). Identification of residues important for agonist recognition and activation in GPR40. J. Biol. Chem. 282, 29248-29255.
73. Sun, Q., Hirasawa, A., Hara, T., Kimura, I., Adachi, T., Awaji, T., Ishiguro, M., Suzuki, T., Miyata, N., and Tsujimoto, G. (2010). Structure-activity relationships of GPR120 agonists based on a docking simulation. Mol. Pharmacol. 78, 804-810.
74. Suzuki, T., Igari, S., Hirasawa, A., Hata, M., Ishiguro, M., Fujieda, H., Itoh, Y., Hirano, T., Nakagawa, H., Ogura, M., Makishima, M., Tsujimoto, G., and Miyata, N. (2008). Identification of G protein-coupled receptor 120-selective agonists derived from PPARgamma agonists. J. Med. Chem. 51, 7640-7644.
75. Talukdar, S., Olefsky, J. M., and Osborn, O. (2011). Targeting GPR120 and other fatty acid-sensing GPCRs ameliorates insulin resistance and inflammatory diseases. Trends Pharmacol. Sci. 32, 543-550.
76. Tan, C. P., Feng, Y., Zhou, Y. P., Eiermann, G. J., Petrov, A., Zhou, C., Lin, S., Salituro, G., Meinke, P., Mosley, R., Akiyama, T. E., Einstein, M., Kumar, S., Berger, J. P., Mills, S. G., Thornberry, N. A., Yang, L., and Howard, A. D. (2008). Selective small-molecule agonists of G protein-coupled receptor 40 promote glucose-dependent insulin secretion and reduce blood glucose in mice. Diabetes 57, 2211-2219.
77. Tanaka, T., Katsuma, S., Adachi, T., Koshimizu, T. A., Hirasawa, A., and Tsujimoto, G. (2008a). Free fatty acids induce cholecystokinin secretion through GPR120. Naunyn Schmiedebergs Arch. Pharmacol. 377, 523-527.
78. Tanaka, T., Yano, T., Adachi, T., Koshimizu, T. A., Hirasawa, A., and Tsujimoto, G. (2008b). Cloning and characterization of the rat free fatty acid receptor GPR120: in vivo effect of the natural ligand on GLP-1 secretion and proliferation of pancreatic beta cells. Naunyn Schmiedebergs Arch. Pharmacol. 377, 515-522.
79. Tikhonova, I. G., Sum, C. S., Neumann, S., Thomas, C. J., Raaka, B. M., Costanzi, S., and Gershengorn, M. C. (2007). Bidirectional, iterative approach to the structural delineation of the functional "chemoprint" in GPR40 for agonist recognition. J. Med. Chem. 50, 2981-2989.
80. 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., and Nakao, K. (2006). 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. Diabetologia 49, 962-968.
81. 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., and Nakao, K. (2005). GPR40 gene expression in human pancreas and insulinoma. Biochem. Biophys. Res. Commun. 338, 1788-1790.
82. Tsujihata, Y., Ito, R., Suzuki, M., Harada, A., Negoro, N., Yasuma, T., Momose, Y., and Takeuchi, K. (2011). TAK-875, an orally available G protein-coupled receptor 40/free fatty acid receptor 1 agonist, enhances glucose-dependent insulin secretion and improves both postprandial and fasting hyperglycemia in type 2 diabetic rats. J. Pharmacol. Exp. Ther. 339, 228-237.
83. Varga, T., Czimmerer, Z., and Nagy, L. (2011). PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation. Biochim. Biophys. Acta 1812, 1007-1022.
84. Vettor, R., Granzotto, M., De Stefani, D., Trevellin, E., Rossato, M., Farina, M. G., Milan, G., Pilon, C., Nigro, A., Federspil, G., Vigneri, R., Vitiello, L., Rizzuto, R., Baratta, R., and Frittitta, L. (2008). Loss-of-function mutation of the GPR40 gene associates with abnormal stimulated insulin secretion by acting on intracellular calcium mobilization. J. Clin. Endocrinol. Metab. 93, 3541-3550.
85. Viswanathan, P., Marcinak, J., Cao, C., Xie, B., Vakilynejad, M., and Leifke, E. (2011). A randomized, double-blind, placebo-and active-controlled, dose-ranging study to determine the efficacy and safety of the novel GPR40 agonist TAK-875 in subjects with T2DM. Presented at 71st American Diabetes Association meeting (oral presentation 0134-LBOR), San Diego, CA.
86. Wild, S., Roglic, G., Green, A., Sicree, R., and King, H. (2004). Global prevalence of diabetes - estimates for the year 2000 and projections for 2030. Diabetes Care 27, 1047-1053.
87. Wu, P., Yang, L., and Shen, X. (2010). The relationship between GPR40 and lipotoxicity of the pancreatic beta-cells as well as the effect of pioglitazone. Biochem. Biophys. Res. Commun. 403, 36-39.
88. Yaney, G. C., and Corkey, B. E. (2003). Fatty acid metabolism and insulin secretion in pancreatic beta cells. Diabetologia 46, 1297-1312.
89. Zhang, X., Yan, G., Li, Y., Zhu, W., and Wang, H. (2010). DC260126, a small-molecule antagonist of GPR40, improves insulin tolerance but not glucose tolerance in obese Zucker rats. Biomed. Pharmacother. 64, 647-651.
90. Zhou, C., Tang, C., Chang, E., Ge, M., Lin, S., Cline, E., Tan, C. P., Feng, Y., Zhou, Y. P., Eiermann, G. J., Petrov, A., Salituro, G., Meinke, P., Mosley, R., Akiyama, T. E., Einstein, M., Kumar, S., Berger, J., Howard, A. D., Thornberry, N., Mills, S. G., and Yang, L. (2010). Discovery of 5-aryloxy-2,4-thiazolidinediones as potent GPR40 agonists. Bioorg. Med. Chem. Lett. 20, 1298-1301.
91. Zwier, J. M., Roux, T., Cottet, M., Durroux, T., Douzon, S., Bdioui, S., Gregor, N., Bourrier, E., Oueslati, N., Nicolas, L., Tinel, N., Boisseau, C., Yverneau, P., Charrier-Savournin, F., Fink, M., and Trinquet, E. (2010). A fluorescent ligand-binding alternative using Tag-lite(R) technology. J. Biomol. Screen 15, 1248-1259.