G protein-coupled receptors: signalling and regulation by lipid agonists for improved glucose homoeostasis
详细信息 查看全文
- 作者：Brian M. Moran ; Peter R. Flatt ; Aine M. McKillop
- 关键词：G protein ; coupled receptor ; Lipid agonists ; Insulin secretion ; Type 2 diabetes ; Fatty acids
- 刊名：Acta Diabetologica
- 出版年：2016
- 出版时间：April 2016
- 年：2016
- 卷：53
- 期：2
- 页码：177-188
- 全文大小：867 KB
- 参考文献：1.Zhang Z, Wu J, Yu J, Xiao J (2012) A brief review on the evolution of GPCR: conservation and diversification. Open J Genet 2:11–17
2.Insel PA, Tang CM, Hahntow I, Michel MC (2007) Impact of GPCRs in clinical medicine: genetic variants and drug targets. Biochim Biophys Acta 1768:994–1005PubMed PubMedCentral
3.Lin HH (2013) G-protein-coupled receptors and their (Bio) chemical significance win 2012 Nobel Prize in chemistry. Biomed J 36:118–124PubMed
4.Davies MN, Secker A, Halling-Brown M et al (2008) GPCRTree: online hierarchical classification of GPCR function. BMC Res Notes 1:67PubMed PubMedCentral
5.Nordstorm KJV, Lagerstrom MC, Waller LMJ, Fredriksson R, Schioth HB (2009) The secretin GPCRs descended from the family of adhesion GPCRs. Mol Biol Evol 26:71–84
6.Beinborn M (2006) Class B GPCRs: a hidden agonist within? Mol Pharmacol 70:1–4PubMed
7.Mertens I, Vandingenen A, Johnson EC et al (2005) PDF receptor signalling in Drosophila contributes to both circadian and geotactic behaviours. Neuron 48:213–219PubMed
8.Chun L, Zhang WH, Liu JF (2012) Structure and ligand recognition of class C GPCRs. Acta Pharmacol Sin 33:312–323PubMed PubMedCentral
9.Xue C, Hsueh YP, Heitman J (2008) Magnificent seven: roles of G protein-coupled receptors in extracellular sensing in fungi. FEMS Microbiol Rev 32:1010–1032PubMed PubMedCentral
10.Sarkar FH, Li Y, Wang Z, Kong D (2010) The role of nutraceuticals in the regulation of Wnt and Hedgehog signaling in cancer. Cancer Metastasis Rev 29:383–394PubMed PubMedCentral
11.Abdulkhalek S, Hrynyk M, Szewczuk MR (2013) A novel G-protein-coupled receptor-signaling platform and its targeted translation in human disease. Res Rep Biochem 3:17–30
12.Lattin J, Zidar DA, Schroder K, Kellie S, Hume DA, Sweet MJ (2007) G-protein-coupled receptor expression, function, and signalling in macrophages. J Leukoc Biol 82:16–32PubMed
13.Tilley DG (2011) G protein-dependent and G protein-independent signalling pathways and their impact on cardiac function. Cir Res 109:217–230
14.Ahren B (2009) Islet G protein-coupled receptors as potential targets for treatment of type 2 diabetes. Nat Rev Drug Discov 8:369–385PubMed
15.Patel TB (2004) Single transmembrane spanning heterotrimeric G protein-coupled receptors and their signalling cascades. Pharmacol Rev 56:371–385PubMed
16.Amisten S, Salehi A, Rorsman P, Jones PM, Persaud SJ (2013) An atlas and functional analysis of G-protein coupled receptors in human islets of Langerhans. Pharmacol Ther 139:359–391PubMed
17.Vangaveti V, Shashidhar V, Jarrod G, Baune BT, Kennedy RL (2010) Free fatty acid receptors: emerging targets for treatment of diabetes and its complications. Ther Adv Endocrinol Metab 1:165–175PubMed PubMedCentral
18.Moran BM, Abdel-Wahab YH, Vasu S, Flatt PR, McKillop AM (2015) GPR39 receptors and actions of trace metals on pancreatic beta cell function and glucose homoeostasis. Acta Diabetol (Epub ahead of print)
19.Juan-Picó P, Fuentes E, Bermúdez-Silva FJ et al (2006) Cannabinoid receptors regulate Ca(2+) signals and insulin secretion in pancreatic beta-cell. Cell Calcium 39:155–162PubMed
20.Kang SU (2013) GPR119 agonists: a promising approach for T2DM treatment? A SWOT analysis of GPR119. Drug Discov Today 18:1309–1315PubMed
21.Tanaka T, Yano T, Adachi T, Koshimizu T, Hirasawa A, Tsujimoto G (2008) 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. N-S Arch Pharmacol 377:515–522
22.Parker HE, Habib AM, Rogers GJ, Gribble FM, Reimann F (2009) Nutrient-dependent secretion of glucose-dependent insulinotropic polypeptide from primary murine K cells. Diabetologia 52:289–298PubMed PubMedCentral
23.Tanaka T, Katsuma S, Adachi T, Koshimizu TA, Hirasawa A, Tsujimoto G (2008) Free fatty acids induce cholecystokinin secretion through GPR120. N-S Arch Pharmacol 377:523–527
24.Holst JJ, Vilsbøll T, Deacon CF (2009) The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol 297:127–136PubMed
25.Burant CF (2013) Activation of GPR40 a therapeutic target for the treatment of type 2 diabetes. Diabetes Care 36:175–179
26.Tazoe H, Otomo Y, Kaji I, Tanaka R, Karaki SI, Kuwahara A (2008) Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions. J Physiol Pharmacol 59:251–262PubMed
27.Watson S, Brown AJH, Holliday ND (2012) Differential signalling by splice variants of the human free fatty acid receptor GPR120. Mol Pharmacol 81:631–642PubMed PubMedCentral
28.Brownlie R, Mayers RM, Pierce JA, Marley AE, Smith DM (2008) The long-chain fatty acid receptor, GPR40, and glucolipotoxicity: investigations using GPR40-knockout mice. Biochem Soc Trans 36:950–954PubMed
29.Stoddart LA, Smith NJ, Milligan G (2008) International Union of Pharmacology LXXI. Free fatty acid receptors FFA1, -2, and -3: pharmacology and pathophysiological functions. Pharmacol Rev 60:405–417PubMed
30.Ferdaoussi M, Bergeron V, Kebede M, Mancini A, Alquier T, Poitout V (2012) Free fatty acid receptor 1: a new drug target for type 2 diabetes? Can J Diabetes 36:275–280
31.Wang L, Zhao Y, Gui B et al (2011) Acute stimulation of glucagon secretion by linoleic acid results from GPR40 activation and [Ca2+]i increase in pancreatic islet α-cells. J Endocrinol 210:173–179PubMed
32.Ferdaoussi M, Bergeron V, Zarrouki B et al (2012) G protein-coupled receptor (GPR) 40-dependent potentiation of insulin secretion in mouse islets is mediated by protein kinase D1. Diabetologia 55:2682–2692PubMed PubMedCentral
33.Seljeset S, Siehler S (2012) Receptor-specific regulation of ERK1/2 activation by members of the “free fatty acid receptor” family. J Recept Signal Transduct Res 32:196–201PubMed
34.Nagasumi K, Esaki R, Iwachidow K et al (2009) Overexpression of GPR40 in pancreatic beta-cells augments glucose-stimulated insulin secretion and improves glucose tolerance in normal and diabetic mice. Diabetes 58:1067–1076PubMed PubMedCentral
35.Kebede M, Alquier T, Latour MG, Semache M, Tremblay C, Poitout V (2008) The fatty acid receptor GPR40 plays a role in insulin secretion in vivo after high-fat feeding. Diabetes 57:2432–2437PubMed PubMedCentral
36.Itoh Y, Kawamata Y, Harada M et al (2003) Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature 42:173–176
37.Christiansen E, Watterson KR, Stocker CJ et al (2015) Activity of dietary fatty acids on FFA1 and FFA4 and characterisation of pinolenic acid as a dual FFA1/FFA4 agonist with potential effect against metabolic diseases. Br J Nutr 113:1677–1688PubMed
38.Hauge M, Vestmar MA, Husted AS et al (2015) GPR40 (FFAR1)—combined Gs and Gq signalling in vitro is associated with robust incretin secretagogue action ex vivo and in vivo. Mol Metab 4:3–14PubMed PubMedCentral
39.Sunil V, Verma MK, Oommen AM et al (2014) CNX-011-67, a novel GPR40 agonist, enhances glucose responsiveness, insulin secretion and islet insulin content in n-STZ rats and in islets from type 2 diabetic patients. BMC Pharmacol Toxicol 25:15
40.Yonezawa T, Kurata R, Yoshida K, Murayama MA, Cui X, Hasegawa A (2013) Free fatty acids-sensing G protein-coupled receptors in drug targeting and therapeutics. Curr Med Chem 20:3855–3871PubMed
41.Burant CF, Viswanathan P, Marcinak J et al (2012) TAK-875 versus placebo or glimepiride in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet 379:1403–1411PubMed
42.Kim MH, Seung KG, Park JH, Yanagisawa M, Kim CH (2013) Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. Gastroenterology 145:396–406PubMed
43.Ulven T (2012) Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets. Front Endocinol 3:111
44.Kaji I, Karaki S, Kuwahara A (2014) Short-chain fatty acids receptor and its contribution to glucagon-like peptide-1 release. Digestion 89:31–36PubMed
45.Inoue D, Kimura I, Wakabayashi M et al (2012) Short-chain fatty acid receptor GPR41-mediated activation of sympathetic neurons involves synapsin 2b phosphorylation. FEBS Lett 586:1547–1554PubMed
46.Xiong Y, Miyamoto N, Shibata K et al (2004) Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. Proc Natl Acad Sci USA 101:1045–1050PubMed PubMedCentral
47.Talukdar S, Olefsky J, Osborn O (2011) Targeting GPR120 and other fatty acid sensing GPCRs ameliorates insulin resistance and inflammatory diseases. Trends Pharmacol Sci 32:543–550PubMed PubMedCentral
48.De Vadder F, Kovatcheva-Datchary P, Goncalves D et al (2014) Microbiota-generated metabolites promote metabolic benefits via gut
ain neural circuits. Cell 156:84–96PubMed
49.Topping DL, Clifton PM (2001) Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev 81:1031–1064PubMed
50.Brown AJ, Goldsworthy SM, Barnes AA et al (2003) The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 278:11312–11319PubMed
51.Kimura I, Inoue D, Hirano K, Tsujimoto G (2014) The SCFA receptor GPR43 and energy metabolism. Front Endocrinol 5:85
52.Tolhurst G, Heffron H, Lam YS et al (2012) Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 61:364–371PubMed PubMedCentral
53.Kimura I, Ozawa K, Inoue D et al (2013) The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat Commun 4:1829PubMed PubMedCentral
54.Bjursell M, Admyre T, Göransson M et al (2011) Improved glucose control and reduced body fat mass in free fatty acid receptor 2-deficient mice fed a high-fat diet. Am J Physiol Endocrinol Metab 300:211–220
55.Oka S, Nakajima K, Yamashita A, Kishimoto S, Sugiura T (2007) Identification of GPR55 as a lysophosphatidylinositol receptor. Biochem Biophys Res Commun 362:928–934PubMed
56.Mackie K, Stella N (2006) Cannabinoid receptors and endocannabinoids: evidence for new players. AAPS J 8:298–306
57.Pertwee RG, Howlett AC, Abood ME et al (2010) International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB1 and CB2. Pharmacol Rev 62:588–631PubMed PubMedCentral
58.Ryberg E, Larsson N, Sjögren S et al (2007) The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 152:1092–10101PubMed PubMedCentral
59.Simcocks AC, O’Keefe L, Jenkin KA, Mathai ML, Hryciw DH, McAinch AJ (2013) A potential role for GPR55 in the regulation of energy homeostasis. Drug Discov Today 24:1–7
60.Staton PC, Hatcher JP, Walker DJ et al (2008) The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain. Pain 139:225–236PubMed
61.Whyte LS, Ryberg E, Sims NA et al (2009) The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo. Proc Natl Acad Sci USA 106:16511–16516PubMed PubMedCentral
62.Romero-Zerbo SY, Rafacho A, Diaz-Arteaga A et al (2011) A role for the putative cannabinoid receptor GPR55 in the islets of Langerhans. J Endocrinol 211:177–185PubMed
63.McKillop AM, Moran BM, Abdel-Wahab YHA, Flatt PR (2013) Evaluation of insulin releasing and antihyperglycaemic activities of GPR55 lipid agonists using clonal beta-cells, isolated pancreatic islets and mice. Br J Pharmacol 170:978–990PubMed PubMedCentral
64.Ross RA (2008) The enigmatic pharmacology of GPR55. Trends Pharmacol Sci 30:156–163
65.Sylantyev S, Jensen TP, Ross RA, Rusakov DA (2013) Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses. Proc Natl Acad Sci USA 110:5193–5198PubMed PubMedCentral
66.Vilches-Flores A, Delgado-Buenrostro NL, Navarrete-Vazquez G, Villalobos-Molina R (2010) CB1 cannabinoid receptor expression is regulated by glucose and feeding in rat pancreatic islets. Regul Pept 163:81–87PubMed
67.Kargl J, Brown AJ, Andersen L et al (2013) A selective antagonist reveals a potential role of G protein coupled receptor 55 in platelet and endothelial cell function. J Pharmacol Exp Ther 346:54–66PubMed
68.Moreno-Navarrete JM, Catalán V, Whyte L et al (2012) The L-α-lysophosphatidylinositol/GPR55 system and its potential role in human obesity. Diabetes 61:281–291PubMed PubMedCentral
69.Gasperi V, Dainese E, Oddi S, Sabatucci A, Maccarrone M (2013) GPR55 and its interaction with membrane lipids: comparison with other endocannabinoid-binding receptors. Curr Med Chem 20:64–78PubMed
70.Wu CS, Chen H, Sun H et al (2013) GPR55, a G-protein coupled receptor for lysophosphatidylinositol, plays a role in motor coordination. PLoS One 8:e60314PubMed PubMedCentral
71.McHugh D, Hu SJS, Rimmerman N et al (2010) N-arachidonoylglycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor. BMC Neurosci 11:1–14
72.Díaz-Arteaga A, Vázquez MJ, Vazquez-Martínez R et al (2012) The atypical cannabinoid O-1602 stimulates food intake adiposity in rats. Diabetes Obes Metab 14:234–243PubMed
73.Henstridge CM, Balenga NA, Schröder R et al (2010) GPR55 ligands promote receptor coupling to multiple signalling pathways. Br J Pharmacol 160:604–614PubMed PubMedCentral
74.Bermúdez-Silva FJ, Suárez J, Baixeras E et al (2008) Presence of functional cannabinoid receptors in human endocrine pancreas. Diabetologia 51:476–487PubMed
75.Jones RM, Leonard JN, Buzard DJ, Lehmann J (2009) GPR119 agonists for the treatment of type 2 diabetes. Expert Opin Ther Pat 19:1339–1359PubMed
76.Ning Y, O’Neill K, Lan H et al (2008) Endogenous and synthetic agonists of GPR119 differ in signalling pathways and their effects on insulin secretion in MIN6c4 insulinoma cells. Br J Pharmacol 155:1056–1065PubMed PubMedCentral
77.Fredriksson R, Hoglund PJ, Gloriam DE, Lagerstrom MC, Schioth HB (2003) Seven evolutionarily conserved human rhodopsin G protein-coupled receptors lacking close relatives. FEBS Lett 554:381–388PubMed
78.Soga T, Ohishi T, Matsui T et al (2005) Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor. Biochem Biophys Res Commun 326:744–751PubMed
79.Chu ZL, Jones RM, He H et al (2007) A role for β-cell-expressed G protein-coupled receptor 119 in glycaemic control by enhancing glucose-dependent insulin release. Endocrinology 148:2601–2609PubMed
80.Sakamoto K, Inoue H, Kawakami S et al (2006) Expression and distribution of GPR119 in pancreatic islets of mice and rats: predominant localization in pancreatic polypeptide-secreting PP-cells. Biochem Biophys Res Commun 351:474–480PubMed
81.Ohishi T, Yoshida S (2012) The therapeutic potential of GPR119 agonists for type 2 diabetes. Expert Opin Investig Drugs 21:321–328PubMed
82.Chu Z, Carroll C, Alfonso J et al (2008) A role for intestinal endocrine cell-expressed G protein-coupled receptor 119 in glycaemic control by enhancing glucagon-like peptide-1 and glucose-dependent insulinotropic peptide release. Endocrinology 149:2038–2047PubMed
83.Chepurny OG, Bertinetti D, Diskar M et al (2013) Stimulation of proglucagon gene expression by human GPR119 in enteroendocrine L-cell line GLUTag. Mol Endocrinol 27:1267–1282PubMed PubMedCentral
84.Odori S, Hosoda K, Tomita T et al (2013) GPR119 expression in normal human tissues and islet cell tumors: evidence for its islet-gastrointestinal distribution, expression in pancreatic beta cell and alpha cells, and involvement in islet function. Metabolism 62:70–78PubMed
85.Overton HA, Babbs AJ, Doel SM et al (2006) Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agent. Cell Metab 3:167–175PubMed
86.Lauffer LM, Iakoubov R, Brubaker PL (2009) GPR119 is essential for oleoylethanolamide-induced glucagon-like peptide-1 secretion from the intestinal enteroendocrine L-cells. Diabetes 58:1058–1066PubMed PubMedCentral
87.Cornall LM, Mathai ML, Hryciw DH, McAinch AJ (2013) Is GPR119 agonism an appropriate treatment modality for safe amelioration of metabolic diseases? Expert Opin Investig Drugs 22:487–498PubMed
88.Moran BM, Abdel-Wahab YH, Flatt PR, McKillop AM (2014) Activation of GPR119 by fatty acid agonists augments insulin release from clonal β-cells and isolated pancreatic islets and improves glucose tolerance in mice. Biol Chem 394:453–464
89.Kogure R, Toyama K, Hiyamuta S, Kojima I, Takeda S (2011) 5-Hydroxy-eicosapentaenoic acid is an endogenous GPR119 agonist and enhances glucose-dependent insulin secretion. Biochem Biophys Res Commun 416:58–63PubMed
90.Katz LB, Gambale JJ, Rothenberg PL et al (2012) Effects of JNJ-38431055, a novel GPR119 receptor agonist, in randomised, double-blind, placebo-controlled studies in subjects with type 2 diabetes. Diabetes Obes Metab 14:709–716PubMed
91.Polli JW, Hussey E, Bush M et al (2013) Evaluation of drug interactions of GSK1292263 (a GPR119 agonist) with statins: from in vitro data to clinical study design. Xenobiotica 43:498–508PubMed
92.Kim SR, Kim DH, Park SH et al (2013) In vivo efficacy of HD0471953: a novel GPR119 agonist for the treatment of type 2 diabetes mellitus. J Diabetes Res 2013:1–6
93.Cox HM, Tough IR, Woolston AM et al (2010) Peptide YY is critical for acylethanolamide receptor GPR119-induced activation of gastrointestinal mucosal responses. Cell Metab 11:532–542PubMed PubMedCentral
94.Yoshida S, Ohishi T, Matsui T, Shibasaki M (2010) Identification of a novel GPR119 agonist, AS1269574, with in vitro and in vivo glucose-stimulated insulin secretion. Biochem Biophys Res Commun 400:437–441PubMed
95.Yoshida S, Tanaka H, Oshima H et al (2010) AS1907417, a novel GPR119 agonist, as an insulinotropic and β-cell preservative agent for the treatment of type 2 diabetes. Biochem Biophys Res Commun 400:745–751PubMed
96.Yoshida S, Ohishi T, Matsui T et al (2011) The role of small molecule GPR119 agonist, AS-1535907, in glucose-stimulated insulin secretion and pancreatic β-cell function. Diabetes Obes Metab 13:34–41PubMed
97.Paulsen SJ, Larsen LK, Hansen G, Chelur S, Larsen PJ, Vrang N (2014) Expression of the fatty acid receptor GPR120 in the gut of diet-induced-obese rats and its role in GLP-1 secretion. PLoS One 9:e88227PubMed PubMedCentral
98.Hirasawa A, Tsumaya K, Awaji T et al (2005) Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat Med 11:90–94PubMed
99.Hirasawa A, Hara T, Katsuma S, Adachi T, Tsujimoto G (2008) Free fatty acid receptors and drug discovery. Biol Pharm Bull 31:1847–1851PubMed
100.Miyauchi S, Hirasawa A, Iga T et al (2009) Distribution and regulation of protein expression of the free fatty acid receptor GPR120. N-S Arch Pharmacol 379:427–434
101.Ichimura A, Hirasawa A, Poulain-Godefroy O et al (2012) Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and humans. Nature 483:350–357PubMed
102.Moran BM, Abdel-Wahab YH, Flatt PR, McKillop AM (2014) Evaluation of the insulin-releasing and glucose-lowering effects of GPR120 activation in pancreatic β-cells. Diabetes Obes Metab 16:1128–1139PubMed
103.Kebede MA, Alquier T, Latour MG, Poitout V (2009) Lipid receptors and islet function: therapeutic implications? Diabetes Obes Metab 11:10–20PubMed PubMedCentral
104.Stone VM, Dhayal S, Brocklehurst KJ et al (2014) GPR120 (FFAR4) is preferentially expressed in pancreatic delta cells and regulates somatostatin secretion from murine islets of Langerhans. Diabetologia 57:1182–1191PubMed PubMedCentral
105.Iakoubov R, Izzo A, Yeung A, Whiteside CI, Brubaker PL (2007) Protein Kinase Czeta is required for oleic acid-induced secretion of glucagon-like peptide-1 by intestinal endocrine L cells. Endocrinology 148:1089–1098PubMed
106.Gotoh C, Hong YH, Iga T et al (2007) The regulation of adipogenesis through GPR120. Biochem Biophys Res Commun 354:591–597PubMed
107.Taneera J, Lang S, Sharma A et al (2012) A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets. Cell Metab 16:122–134PubMed
108.Oh DY, Talukdar S, Bae EJ et al (2010) GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142:687–698PubMed PubMedCentral
109.Katsuma S, Hatae N, Yano T et al (2005) Free fatty acids inhibits serum deprivation-induced apoptosis through GPR120 in a murine enteroendocrine cell line STC-1. J Biol Chem 280:19507–19515PubMed
110.Hara T, Hirasawa A, Sun Q et al (2009) Novel selective ligands for free fatty acid receptors GPR120 and GPR40. N-S Arch Pharmacol 380:247–255
111.Shimpukade B, Hudson BD, Hovgaard CK, Milligan G, Ulven T (2012) Discovery of a potent and selective GPR120 agonist. J Med Chem 55:4511–4515PubMed
112.Gorjao R, Azevedo-Martins AK, Rodriques HG et al (2009) Comparative effects of DHA and EPA on cell function. Pharmacol Ther 122:56–64PubMed
113.Burdge GC, Calder PC (2005) Conversion of alpha-linolenic acid to longer-chain polyunsaturated fatty acids in human adults. Reprod Nutr Dev 45:581–597PubMed
114.Suzuki T, Igari S, Hirasawa A et al (2008) Identification of G protein-coupled receptor 120-selective agonists derived from PPAR gamma agonists. J Med Chem 51:7640–7644PubMed
115.Hudson BD, Shimpukade B, Mackenzie AE et al (2013) The pharmacology of a potent and selective agonist, TUG-891, demonstrates both potential opportunity and possible challenges to therapeutic agonism of FAR4 (GPR120). Mol Pharmacol 84:1–54
116.Briscoe CP, Peat AJ, McKeown SC et al (2006) Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small agonist. Br J Pharmacol 148:619–628PubMed PubMedCentral
117.Morishita M, Tanaka T, Shida T, Takayama K (2008) Usefulness of colon targeted DHA and EPA as novel diabetes medications that promote intrinsic GLP-1 secretions. J Control Release 132:99–104PubMed
118.Li S, Sun Y, Liang CP et al (2009) Defective phagocytosis of apoptotic cells by macrophages in atherosclerotic lesions of ob/ob mice and reversal by a fish oil diet. Cir Res 105:1072–1082 - 作者单位：Brian M. Moran (1)
Peter R. Flatt (1)
Aine M. McKillop (1)
1. SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Cromore Road, Coleraine, BT52 1SA, Northern Ireland, UK - 刊物类别：Medicine
- 刊物主题：Medicine & Public Health
Internal Medicine
Diabetes
Metabolic Diseases - 出版者：Springer Milan
- ISSN：1432-5233
文摘
G protein-coupled receptors (GPCRs) play a pivotal role in cell signalling, controlling many processes such as immunity, growth, cellular differentiation, neurological pathways and hormone secretions. Fatty acid agonists are increasingly recognised as having a key role in the regulation of glucose homoeostasis via stimulation of islet and gastrointestinal GPCRs. Downstream cell signalling results in modulation of the biosynthesis, secretion, proliferation and anti-apoptotic pathways of islet and enteroendocrine cells. GPR40 and GPR120 are activated by long-chain fatty acids (>C12) with both receptors coupling to the Gαq subunit that activates the Ca2+-dependent pathway. GPR41 and GPR43 are stimulated by short-chain fatty acids (C2–C5), and activation results in binding to Gαi that inhibits the adenylyl cyclase pathway attenuating cAMP production. In addition, GPR43 also couples to the Gαq subunit augmenting intracellular Ca2+ and activating phospholipase C. GPR55 is specific for cannabinoid endogenous agonists (endocannabinoids) and non-cannabinoid fatty acids, which couples to Gα12/13 and Gαq proteins, leading to enhancing intracellular Ca2+, extracellular signal-regulated kinase 1/2 (ERK) phosphorylation and Rho kinase. GPR119 is activated by fatty acid ethanolamides and binds to Gαs utilising the adenylate cyclase pathway, which is dependent upon protein kinase A. Current research indicates that GPCR therapies may be approved for clinical use in the near future. This review focuses on the recent advances in preclinical diabetes research in the signalling and regulation of GPCRs on islet and enteroendocrine cells involved in glucose homoeostasis.