An acetate-specific GPCR, FFAR2, regulates insulin secretion

Molecular Endocrinology

Volumn 29, Issue 7, 2015, Pages 1055-1066

  Priyadarshini, Medha ^a   Villa, Stephanie R ^a   Fuller, Miles ^a   Wicksteed, Barton ^b   Mackay, Charles R ^c   Alquier, Thierry ^d   Poitout, Vincent ^d   Mancebo, Helena ^e   Mirmira, Raghavendra G ^f   Gilchrist, Annette ^g   Layden, Brian T ^a,h  

^a NORTHWESTERN UNIVERSITY   (United States)

^b The University of Chicago ^*  (United States)

^c MONASH UNIVERSITY   (Australia)

^d CENTRE HOSPITALIER DE L UNIVERSITÉ DE MONTRÉAL   (Canada)

^e Multispan Inc   (United States)

^f INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^g MIDWESTERN UNIVERSITY   (United States)

^h JESSE BROWN VA MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETIC ACID; FREE FATTY ACID RECEPTOR 2; G PROTEIN COUPLED RECEPTOR; UNCLASSIFIED DRUG; ACETIC ACID DERIVATIVE; CELL SURFACE RECEPTOR; FFAR2 PROTEIN, MOUSE; G-PROTEIN COUPLED RECEPTOR 43, HUMAN; GUANINE NUCLEOTIDE BINDING PROTEIN ALPHA SUBUNIT; INSULIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CALCIUM MOBILIZATION; CONTROLLED STUDY; EX VIVO STUDY; GLUCOSE HOMEOSTASIS; GLUCOSE STIMULATED INSULIN SECRETION; HYPERGLYCEMIA; IN VIVO STUDY; INSULIN RELEASE; LIPID DIET; MALE; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; PHENOTYPE; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; WILD TYPE; AGONISTS; ANIMAL; C57BL MOUSE; DEFICIENCY; DRUG EFFECTS; GLUCOSE CLAMP TECHNIQUE; GLUCOSE TOLERANCE TEST; HUMAN; KNOCKOUT MOUSE; METABOLISM; SECRETION (PROCESS); SPECIES DIFFERENCE;

MUS; RODENTIA;

ACETATES; ANIMALS; DIET, HIGH-FAT; GLUCOSE CLAMP TECHNIQUE; GLUCOSE TOLERANCE TEST; GTP-BINDING PROTEIN ALPHA SUBUNITS, GQ-G11; HUMANS; INSULIN; MALE; MICE, INBRED C57BL; MICE, KNOCKOUT; PHENOTYPE; RECEPTORS, CELL SURFACE; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION; SPECIES SPECIFICITY;

EID: 84936097852     PISSN: 08888809     EISSN: 19449917     Source Type: Journal    
DOI: 10.1210/me.2015-1007     Document Type: Article

References (44)

1. Layden BT, Angueira AR, Brodsky M, Durai V, Lowe WL Jr. Short chain fatty acids and their receptors: new metabolic targets. Transl Res. 2013;161(3):131–140.
2. Johnston CS, Kim CM, Buller AJ. Vinegar improves insulin sensitivity to a high-carbohydrate meal in subjects with insulin resistance or type 2 diabetes. Diabetes Care. 2004;27(1):281–282.
3. Johnston CS, Steplewska I, Long CA, Harris LN, Ryals RH. Examination of the antiglycemic properties of vinegar in healthy adults. Ann Nutr Metab. 2010;56(1):74–79.
4. White AM, Johnston CS. Vinegar ingestion at bedtime moderates waking glucose concentrations in adults with well-controlled type 2 diabetes. Diabetes Care. 2007;30(11):2814–2815.
5. Kondo T, Kishi M, Fushimi T, Ugajin S, Kaga T. Vinegar intake reduces body weight, body fat mass, and serum triglyceride levels in obese Japanese subjects. Biosci Biotechnol Biochem. 2009;73(8): 1837–1843.
6. Shah JH, Wongsurawat N, Aran PP. Effect of ethanol on stimulusinduced insulin secretion and glucose tolerance. A study of mechanisms. Diabetes. 1977;26(4):271–277.
7. Patel DG, Singh SP. Effect of ethanol and its metabolites on glucose mediated insulin release from isolated islets of rats. Metabolism. 1979;28(1):85–89.
8. Yamashita H, Fujisawa K, Ito E, et al. Improvement of obesity and glucose tolerance by acetate in type 2 diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats. Biosci Biotechnol Biochem. 2007; 71(5):1236–1243.
9. Brown AJ, Goldsworthy SM, Barnes AA, et al. The orphan G protein- coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem. 2003; 278(13):11312–11319.
10. Priyadarshini M, Thomas A, Reisetter AC, et al. Maternal shortchain fatty acids are associated with metabolic parameters in mothers and newborns. Transl Res. 2014;164(2):153–157.
11. Bjursell M, Admyre T, Göransson M, et al. 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. 2011; 300(1):E211–E220.
12. Tolhurst G, Heffron H, Lam YS, et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR 2. Diabetes. 2012;61(2):364–371.
13. Kimura I, Ozawa K, Inoue D, et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR 43. Nat Commun. 2013;4:1829.
14. Tang C, Ahmed K, Gille A, et al. Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes. Nat Med. 2015;21(2):173–177.
15. Layden BT, Durai V, Newman MV, et al. Regulation of pancreatic islet gene expression in mouse islets by pregnancy. J Endocrinol. 2010;207(3):265–279.
16. Leonard J, Chu ZL, Bruce MA, Boatman PD. Pat PCT/US2005/ 039551. WO 2006/ 052566. A2 2006.
17. Rieck S, White P, Schug J, et al. The transcriptional response of the islet to pregnancy in mice. Mol Endocrinol. 2009;23:1702–1712.
18. Keller MP, Choi Y, Wang P, et al. A gene expression network model of type 2 diabetes links cell cycle regulation in islets with diabetes susceptibility. Genome Res. 2008;18(5):706–716.
19. Prentki M, Matschinsky FM, Madiraju SR. Metabolic signaling in fuel-induced insulin secretion. Cell Metab. 2013;18(2):162–185.
20. Le Poul E, Loison C, Struyf S, et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem. 2003;278(28):25481–25489.
21. Tiengo A, Valerio A, Molinari M, Meneghel A, Lapolla A. Effect of ethanol, acetaldehyde, and acetate on insulin and glucagon secretion in the perfused rat pancreas. Diabetes. 1981;30(9):705–709.
22. Ximenes HM, Hirata AE, Rocha MS, Curi R, Carpinelli AR. Propionate inhibits glucose-induced insulin secretion in isolated rat pancreatic islets. Cell Biochem Funct. 2007;25(2):173–178.
23. Montague W, Taylor KW. Regulation of insulin secretion by short chain fatty acids. Nature. 1968;217(5131):853.
24. Priyadarshini M, Layden BT. FFAR3 modulates insulin secretion and global gene expression in mouse islets. Islets. 2015. DOI: 10.1080/19382014.2015.1045182.
25. Burant CF, Viswanathan P, Marcinak J, et al. TAK-875 versus placebo or glimepiride in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2012; 379(9824):1403–1411.
26. Araki T, Hirayama M, Hiroi S, Kaku K. GPR40-induced insulin secretion by the novel agonist TAK-875: first clinical findings in patients with type 2 diabetes. Diabetes Obes Metab. 2012;14(3): 271–278.
27. Ahrén B. Islet G protein-coupled receptors as potential targets for treatment of type 2 diabetes. Nat Rev Drug Discov. 2009;8(5): 369–385.
28. Maslowski KM, Vieira AT, Ng A, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR 43. Nature. 2009;461(7268):1282–1286.
29. Fergusson G, Ethier M, Guévremont M, et al. Defective insulin secretory response to intravenous glucose in C57Bl/6J compared to C57Bl/6N mice. Mol Metab. 2014;3(9):848–854.
30. Chen X, Zhang X, Larson CS, Baker MS, Kaufman DB. In vivo bioluminescence imaging of transplanted islets and early detection of graft rejection. Transplantation. 2006;81(10):1421–1427.
31. Hong YH, Nishimura Y, Hishikawa D, et al. Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR 43. Endocrinology. 2005;146(12):5092–5099.
32. Whittle BJ, Silverstein AM, Mottola DM, Clapp LH. Binding and activity of the prostacyclin receptor (IP) agonists, treprostinil and iloprost, at human prostanoid receptors: treprostinil is a potent DP1 and EP2 agonist. Biochem Pharmacol. 2012;84(1):68–75.
33. Winzell MS, Ahrén B. G-protein-coupled receptors and islet function- implications for treatment of type 2 diabetes. Pharmacol Ther. 2007;116(3):437–448.
34. Pomare EW, Branch WJ, Cummings JH. Carbohydrate fermentation in the human colon and its relation to acetate concentrations in venous blood. J Clin Invest. 1985;75(5):1448–1454.
35. Schmidt J, Smith NJ, Christiansen E, et al. Selective orthosteric free fatty acid receptor 2 (FFA2) agonists: identification of the structural and chemical requirements for selective activation of FFA2 versus FFA 3. J Biol Chem. 2011;286(12):10628–10640.
36. Lee T, Schwandner R, Swaminath G, et al. Identification and functional characterization of allosteric agonists for the G protein-coupled receptor FFA 2. Mol Pharmacol. 2008;74(6):1599–1609.
37. Wang Y, Jiao X, Kayser F, et al. The first synthetic agonists of FFA2: discovery and SAR of phenylacetamides as allosteric modulators. Bioorg Med Chem Lett. 2010;20(2):493–498.
38. Hudson BD, Tikhonova IG, Pandey SK, Ulven T, Milligan G. Extracellular ionic locks determine variation in constitutive activity and ligand potency between species orthologs of the free fatty acid receptors FFA2 and FFA 3. J Biol Chem. 2012;287(49):41195–41209.
39. Kimple ME, Joseph JW, Bailey CL, et al. G_z negatively regulates insulin secretion and glucose clearance. J Biol Chem. 2008;283(8): 4560–4567.
40. Daaka Y, Luttrell LM, Lefkowitz RJ. Switching of the coupling of the _2-adrenergic receptor to different G proteins by protein kinase A. Nature. 1997;390(6655):88–91.
41. Xiao RP. β-Adrenergic signaling in the heart: dual coupling of the β2-adrenergic receptor to G(s) and G(i) proteins. Sci STKE. 2001; 2001(104):re15.
42. Sawzdargo M, George SR, Nguyen T, Xu S, Kolakowski LF, O’Dowd BF. A cluster of four novel human G protein-coupled receptor genes occurring in close proximity to CD22 gene on chromosome 19q13. 1. Biochem Biophys Res Commun. 1997;239(2): 543–547.
43. Dewulf EM, Cani PD, Neyrinck AM, et al. Inulin-type fructans with prebiotic properties counteract GPR43 overexpression and PPARγ- related adipogenesis in the white adipose tissue of high-fat diet-fed mice. J Nutr Biochem. 2011;22(8):712–722.
44. Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58(4):773–795.