SCFA Receptors in Pancreatic β Cells: Novel Diabetes Targets?

Overview

Journal Trends Endocrinol Metab

Specialty Endocrinology

Date 2016 Apr 20

PMID 27091493

Citations 52

Authors

Medha Priyadarshini

Barton Wicksteed

Gary E Schiltz

Annette Gilchrist

Brian T Layden

Affiliations

Soon will be listed here.

Abstract

Nutrient sensing receptors are key metabolic mediators of responses to dietary and endogenously derived nutrients. These receptors are largely G-protein-coupled receptors (GPCRs) and many are gaining significant interest as drug targets with a potential therapeutic role in metabolic diseases. A distinct subclass of nutrient sensing GPCRs, two short chain fatty acid (SCFA) receptors (FFA2 and FFA3) are uniquely responsive to gut microbiota derived nutrients (such as acetate, propionate, and butyrate). Pharmacological, molecular, and genetic studies have investigated their role in organismal glucose metabolism and recently in pancreatic β cell biology. Here, we summarize the present knowledge on the role of these receptors as metabolic sensors in β cell function and physiology, revealing new therapeutic opportunities for type 2 diabetes.

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References

Rieck S, White P, Schug J, Fox A, Smirnova O, Gao N . The transcriptional response of the islet to pregnancy in mice. Mol Endocrinol. 2009; 23(10):1702-12. PMC: 2754894. DOI: 10.1210/me.2009-0144. View

Schmidt J, Smith N, Christiansen E, Tikhonova I, Grundmann M, Hudson B . Selective orthosteric free fatty acid receptor 2 (FFA2) agonists: identification of the structural and chemical requirements for selective activation of FFA2 versus FFA3. J Biol Chem. 2011; 286(12):10628-40. PMC: 3060514. DOI: 10.1074/jbc.M110.210872. View

Priyadarshini M, Villa S, Fuller M, Wicksteed B, Mackay C, Alquier T . An Acetate-Specific GPCR, FFAR2, Regulates Insulin Secretion. Mol Endocrinol. 2015; 29(7):1055-66. PMC: 4484778. DOI: 10.1210/me.2015-1007. View

Geuking M, McCoy K, Macpherson A . Metabolites from intestinal microbes shape Treg. Cell Res. 2013; 23(12):1339-40. PMC: 3847568. DOI: 10.1038/cr.2013.125. View

McNelis J, Lee Y, Mayoral R, van der Kant R, Johnson A, Wollam J . GPR43 Potentiates β-Cell Function in Obesity. Diabetes. 2015; 64(9):3203-17. PMC: 4542437. DOI: 10.2337/db14-1938. View

Layden B, Angueira A, Brodsky M, Durai V, Lowe Jr W . Short chain fatty acids and their receptors: new metabolic targets. Transl Res. 2012; 161(3):131-40. DOI: 10.1016/j.trsl.2012.10.007. View

Ximenes H, Hirata A, Rocha M, Curi R, Carpinelli A . Propionate inhibits glucose-induced insulin secretion in isolated rat pancreatic islets. Cell Biochem Funct. 2006; 25(2):173-8. DOI: 10.1002/cbf.1297. View

Prentki M, Matschinsky F, Murthy Madiraju S . Metabolic signaling in fuel-induced insulin secretion. Cell Metab. 2013; 18(2):162-85. DOI: 10.1016/j.cmet.2013.05.018. View

Kim M, Kang S, Park J, Yanagisawa M, Kim C . Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. Gastroenterology. 2013; 145(2):396-406.e1-10. DOI: 10.1053/j.gastro.2013.04.056. View

10.

Pluznick J, Protzko R, Gevorgyan H, Peterlin Z, Sipos A, Han J . Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proc Natl Acad Sci U S A. 2013; 110(11):4410-5. PMC: 3600440. DOI: 10.1073/pnas.1215927110. View

11.

Taggart A, Kero J, Gan X, Cai T, Cheng K, Ippolito M . (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J Biol Chem. 2005; 280(29):26649-52. DOI: 10.1074/jbc.C500213200. View

12.

McKenzie C, Mackay C, Macia L . GPR43 - A Prototypic Metabolite Sensor Linking Metabolic and Inflammatory Diseases. Trends Endocrinol Metab. 2015; 26(10):511-512. DOI: 10.1016/j.tem.2015.07.009. View

13.

Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K, Maeda T . The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat Commun. 2013; 4:1829. PMC: 3674247. DOI: 10.1038/ncomms2852. View

14.

Bjursell M, Admyre T, Goransson M, Marley A, Smith D, Oscarsson J . 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. 2010; 300(1):E211-20. DOI: 10.1152/ajpendo.00229.2010. View

15.

Wauson E, Lorente-Rodriguez A, Cobb M . Minireview: Nutrient sensing by G protein-coupled receptors. Mol Endocrinol. 2013; 27(8):1188-97. PMC: 3725341. DOI: 10.1210/me.2013-1100. View

16.

Frost G, Sleeth M, Sahuri-Arisoylu M, Lizarbe B, Cerdan S, Brody L . The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat Commun. 2014; 5:3611. PMC: 4015327. DOI: 10.1038/ncomms4611. View

17.

Tang C, Ahmed K, Gille A, Lu S, Grone H, Tunaru S . Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes. Nat Med. 2015; 21(2):173-7. DOI: 10.1038/nm.3779. View

18.

Kasubuchi M, Hasegawa S, Hiramatsu T, Ichimura A, Kimura I . Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients. 2015; 7(4):2839-49. PMC: 4425176. DOI: 10.3390/nu7042839. View

19.

Karnik S, Chen H, McLean G, Heit J, Gu X, Zhang A . Menin controls growth of pancreatic beta-cells in pregnant mice and promotes gestational diabetes mellitus. Science. 2007; 318(5851):806-9. DOI: 10.1126/science.1146812. View

20.

Tolhurst G, Heffron H, Lam Y, Parker H, Habib A, Diakogiannaki E . Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2011; 61(2):364-71. PMC: 3266401. DOI: 10.2337/db11-1019. View