Journal of Cell Communication and Signaling

, Volume 11, Issue 2, pp 105–116 | Cite as

Regulation of pancreatic β-cell function and mass dynamics by prostaglandin signaling

  • Bethany A. Carboneau
  • Richard M. Breyer
  • Maureen Gannon


Prostaglandins (PGs) are signaling lipids derived from arachidonic acid (AA), which is metabolized by cyclooxygenase (COX)-1 or 2 and class-specific synthases to generate PGD2, PGE2, PGF, PGI2 (prostacyclin), and thromboxane A2. PGs signal through G-protein coupled receptors (GPCRs) and are important modulators of an array of physiological functions, including systemic inflammation and insulin secretion from pancreatic islets. The role of PGs in β-cell function has been an active area of interest, beginning in the 1970s. Early studies demonstrated that PGE2 inhibits glucose-stimulated insulin secretion (GSIS), although more recent studies have questioned this inhibitory action of PGE2. The PGE2 receptor EP3 and one of the G-proteins that couples to EP3, GαZ, have been identified as negative regulators of β-cell proliferation and survival. Conversely, PGI2 and its receptor, IP, play a positive role in the β-cell by enhancing GSIS and preserving β-cell mass in response to the β-cell toxin streptozotocin (STZ). In comparison to PGE2 and PGI2, little is known about the function of the remaining PGs within islets. In this review, we discuss the roles of PGs, particularly PGE2 and PGI2, PG receptors, and downstream signaling events that alter β-cell function and regulation of β-cell mass.


β-cell GSIS Proliferation Prostaglandins 



Arachidonic Acid




Exchange Protein Directly Activated by cAMP 2


G-Protein Coupled Receptor


Glucagon-Like Peptide-1


High Fat Diet


Interleukin 1-β


Insulin Tolerance Test


Intraperitoneal Glucose Tolerance Test


c-Jun N-Terminal Kinase


microsomal PGE2 Synthase 1


Non-Steroidal Anti-Inflammatory Drugs


Nuclear Factor κB


Pancreatic and duodenal homeobox 1


Pertussis Toxin


Phosphatidylinositol 3-Kinase


Phospholipase A2




Protein Kinase A


Single Nucleotide Polymorphism




Type 2 Diabetes



We would like to thank members of the Gannon lab for helpful discussions and, in particular, Dr. Raymond Pasek for critical reading of the manuscript. We also thank Dr. R. Paul Robertson for reading and helpful discussions of the manuscript. This work was supported by a Merit Award from the Veterans Administration (Grant 1 I01 BX003744-01) to M.G.


  1. Abramovitz M, Adam M, Boie Y, Carriere M, Denis D, Godbout C, Lamontagne S, Rochette C, Sawyer N, Tremblay NM et al (2000) The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochim Biophys Acta 1483:285–293CrossRefPubMedGoogle Scholar
  2. Ahlgren U, Jonsson J, Jonsson L, Simu K, Edlund H (1998) Beta-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes. Genes Dev 12:1763–1768CrossRefPubMedPubMedCentralGoogle Scholar
  3. Ahren B (2009) Islet G protein-coupled receptors as potential targets for treatment of type 2 diabetes. Nat Rev Drug Discov 8:369–385CrossRefPubMedGoogle Scholar
  4. Akpan JO, Hurley MC, Pek S, Lands WE (1979) The effects of prostaglandins on secretion of glucagon and insulin by the perfused rat pancreas. Can J Biochem 57:540–547CrossRefPubMedGoogle Scholar
  5. Anderson SL, Trujillo JM, McDermott M, Saseen JJ (2012) Determining predictors of response to exenatide in type 2 diabetes. J Am Pharm Assoc 52:466–471CrossRefGoogle Scholar
  6. Arita S, Une S, Ohtsuka S, Kawahara T, Kasraie A, Smith CV, Mullen Y (2001) Increased islet viability by addition of beraprost sodium to collagenase solution. Pancreas 23:62–67CrossRefPubMedGoogle Scholar
  7. Batchu SN, Majumder S, Bowskill BB, White KE, Advani SL, Brijmohan AS, Liu Y, Thai K, Azizi PM, Lee WL et al (2016) Prostaglandin I2 receptor agonism preserves beta-cell function and attenuates albuminuria through nephrin-dependent mechanisms. Diabetes 65:1398–1409CrossRefPubMedGoogle Scholar
  8. Bramswig NC, Everett LJ, Schug J, Dorrell C, Liu C, Luo Y, Streeter PR, Naji A, Grompe M, Kaestner KH (2013) Epigenomic plasticity enables human pancreatic alpha to beta cell reprogramming. J Clin Invest 123:1275–1284CrossRefPubMedPubMedCentralGoogle Scholar
  9. Breyer RM, Bagdassarian CK, Myers SA, Breyer MD (2001) Prostanoid receptors: subtypes and signaling. Annu Rev Pharmacol Toxicol 41:661–690CrossRefPubMedGoogle Scholar
  10. Brill AL, Wisinski JA, Cadena MT, Thompson MF, Fenske RJ, Brar HK, Schaid MD, Pasker RL, Kimple ME (2016) Synergy between Galphaz deficiency and GLP-1 analog treatment in preserving functional beta-cell mass in experimental diabetes. Mol Endocrinol 30:543–556CrossRefPubMedPubMedCentralGoogle Scholar
  11. Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME (1999) Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor. Cell 96:857–868CrossRefPubMedGoogle Scholar
  12. Burke SJ, Collier JJ (2011) The gene encoding cyclooxygenase-2 is regulated by IL-1beta and prostaglandins in 832/13 rat insulinoma cells. Cell Immunol 271:379–384CrossRefPubMedGoogle Scholar
  13. Burr IM, Sharp R (1974) Effects of prostaglandin E1 and of epinephrine on the dynamics of insulin release in vitro. Endocrinology 94:835–839CrossRefPubMedGoogle Scholar
  14. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC (2003) Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 52:102–110CrossRefPubMedGoogle Scholar
  15. Caporarello N, Salmeri M, Scalia M, Motta C, Parrino C, Frittitta L, Olivieri M, Cristaldi M, Avola R, Bramanti V et al (2016) Cytosolic and calcium-independent phospholipases A2 activation and prostaglandins E2 are associated with Escherichia Coli-induced reduction of insulin secretion in INS-1E cells. PLoS One 11:e0159874CrossRefPubMedPubMedCentralGoogle Scholar
  16. Ceddia RP, Lee D, Maulis MF, Carboneau BA, Threadgill DW, Poffenberger G, Milne G, Boyd KL, Powers AC, McGuinness OP et al (2016) The PGE2 EP3 receptor regulates diet-induced adiposity in male mice. Endocrinology 157:220–232CrossRefPubMedGoogle Scholar
  17. Del Prato S, Pulizzi N (2006) The place of sulfonylureas in the therapy for type 2 diabetes mellitus. Metabolism 55:S20–S27CrossRefPubMedGoogle Scholar
  18. Dor Y, Brown J, Martinez OI, Melton DA (2004) Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429:41–46CrossRefPubMedGoogle Scholar
  19. Dutta S, Bonner-Weir S, Montminy M, Wright C (1998) Regulatory factor linked to late-onset diabetes? Nature 392:560CrossRefPubMedGoogle Scholar
  20. Ebstein W (1876) Zur therapie des diabetes mellitus, insbesondere uber die anewendeng des salicylsauren natron bei demselben. Klin Worshensche:337–340Google Scholar
  21. Evans MH, Pace CS, Clements RS Jr (1983) Endogenous prostaglandin synthesis and glucose-induced insulin secretion from the adult rat pancreatic islet. Diabetes 32:509–515CrossRefPubMedGoogle Scholar
  22. Fields TA, Casey PJ (1997) Signalling functions and biochemical properties of pertussis toxin-resistant G-proteins. Biochem J 321(Pt 3):561–571CrossRefPubMedPubMedCentralGoogle Scholar
  23. Fornoni A, Jeon J, Varona Santos J, Cobianchi L, Jauregui A, Inverardi L, Mandic SA, Bark C, Johnson K, McNamara G et al (2010) Nephrin is expressed on the surface of insulin vesicles and facilitates glucose-stimulated insulin release. Diabetes 59:190–199CrossRefPubMedGoogle Scholar
  24. Giugliano D, Di Pinto P, Torella R, Frascolla N, Saccomanno F, Passariello N, D'Onofrio F (1983) A role for endogenous prostaglandin E in biphasic pattern of insulin release in humans. Am J Phys 245:E591–E597Google Scholar
  25. Golson ML, Misfeldt AA, Kopsombut UG, Petersen CP, Gannon M (2010) High fat diet regulation of beta-cell proliferation and beta-cell mass. Open Endocrinol J 4. doi: 10.2174/1874216501004010066
  26. Golson ML, Maulis MF, Dunn JC, Poffenberger G, Schug J, Kaestner KH, Gannon MA (2014) Activated FoxM1 attenuates streptozotocin-mediated beta-cell death. Mol Endocrinol 28:1435–1447CrossRefPubMedPubMedCentralGoogle Scholar
  27. Gunasekaran U, Gannon M (2011) Type 2 diabetes and the aging pancreatic beta cell. Aging (Albany NY) 3:565–575CrossRefGoogle Scholar
  28. Gurgul-Convey E, Lenzen S (2010) Protection against cytokine toxicity through endoplasmic reticulum and mitochondrial stress prevention by prostacyclin synthase overexpression in insulin-producing cells. J Biol Chem 285:11121–11128CrossRefPubMedPubMedCentralGoogle Scholar
  29. Gurgul-Convey E, Hanzelka K, Lenzen S (2012) Mechanism of prostacyclin-induced potentiation of glucose-induced insulin secretion. Endocrinology 153:2612–2622CrossRefPubMedGoogle Scholar
  30. Hata AN, Breyer RM (2004) Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation. Pharmacol Ther 103:147–166CrossRefPubMedGoogle Scholar
  31. Heitmeier MR, Scarim AL, Corbett JA (1997) Interferon-gamma increases the sensitivity of islets of Langerhans for inducible nitric-oxide synthase expression induced by interleukin 1. J Biol Chem 272:13697–13704CrossRefPubMedGoogle Scholar
  32. Heitmeier MR, Kelly CB, Ensor NJ, Gibson KA, Mullis KG, Corbett JA, Maziasz TJ (2004) Role of cyclooxygenase-2 in cytokine-induced beta-cell dysfunction and damage by isolated rat and human islets. J Biol Chem 279:53145–53151CrossRefPubMedGoogle Scholar
  33. Hellstrom-Lindahl E, Danielsson A, Ponten F, Czernichow P, Korsgren O, Johansson L, Eriksson O (2016) GPR44 is a pancreatic protein restricted to the human beta cell. Acta Diabetol 53:413–421CrossRefPubMedGoogle Scholar
  34. Hughes JH, Easom RA, Wolf BA, Turk J, McDaniel ML (1989) Interleukin 1-induced prostaglandin E2 accumulation by isolated pancreatic islets. Diabetes 38:1251–1257CrossRefPubMedGoogle Scholar
  35. Jung KY, Kim KM, Lim S (2014) Therapeutic approaches for preserving or restoring pancreatic beta-cell function and mass. Diabetes Metab J 38:426–436CrossRefPubMedPubMedCentralGoogle Scholar
  36. Kapodistria K, Tsilibary EP, Politis P, Moustardas P, Charonis A, Kitsiou P (2015) Nephrin, a transmembrane protein, is involved in pancreatic beta-cell survival signaling. Mol Cell Endocrinol 400:112–128CrossRefPubMedGoogle Scholar
  37. Kashima Y, Miki T, Shibasaki T, Ozaki N, Miyazaki M, Yano H, Seino S (2001) Critical role of cAMP-GEFII--Rim2 complex in incretin-potentiated insulin secretion. J Biol Chem 276:46046–46053CrossRefPubMedGoogle Scholar
  38. Kelly KL, Laychock SG (1981) Prostaglandin synthesis and metabolism in isolated pancreatic islets of the rat. Prostaglandins 21:759–769CrossRefPubMedGoogle Scholar
  39. Kelly KL, Laychock SG (1984) Activity of prostaglandin biosynthetic pathways in rat pancreatic islets. Prostaglandins 27:925–938CrossRefPubMedGoogle Scholar
  40. Khoo C, Yang J, Weinrott SA, Kaestner KH, Naji A, Schug J, Stoffers DA (2012) Research resource: the pdx1 cistrome of pancreatic islets. Mol Endocrinol 26:521–533CrossRefPubMedPubMedCentralGoogle Scholar
  41. Kimple ME, Nixon AB, Kelly P, Bailey CL, Young KH, Fields TA, Casey PJ (2005) A role for G(z) in pancreatic islet beta-cell biology. J Biol Chem 280:31708–31713CrossRefPubMedGoogle Scholar
  42. Kimple ME, Joseph JW, Bailey CL, Fueger PT, Hendry IA, Newgard CB, Casey PJ (2008) Galphaz negatively regulates insulin secretion and glucose clearance. J Biol Chem 283:4560–4567CrossRefPubMedGoogle Scholar
  43. Kimple ME, Moss JB, Brar HK, Rosa TC, Truchan NA, Pasker RL, Newgard CB, Casey PJ (2012) Deletion of GalphaZ protein protects against diet-induced glucose intolerance via expansion of beta-cell mass. J Biol Chem 287:20344–20355CrossRefPubMedPubMedCentralGoogle Scholar
  44. Kimple ME, Keller MP, Rabaglia MR, Pasker RL, Neuman JC, Truchan NA, Brar HK, Attie AD (2013) Prostaglandin E2 receptor, EP3, is induced in diabetic islets and negatively regulates glucose- and hormone-stimulated insulin secretion. Diabetes 62:1904–1912CrossRefPubMedPubMedCentralGoogle Scholar
  45. Kimple ME, Neuman JC, Linnemann AK, Casey PJ (2014) Inhibitory G proteins and their receptors: emerging therapeutic targets for obesity and diabetes. Exp Mol Med 46:e102CrossRefPubMedPubMedCentralGoogle Scholar
  46. Kitamura T, Nakae J, Kitamura Y, Kido Y, Biggs WH 3rd, Wright CV, White MF, Arden KC, Accili D (2002) The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. J Clin Invest 110:1839–1847CrossRefPubMedPubMedCentralGoogle Scholar
  47. Konheim YL, Wolford JK (2003) Association of a promoter variant in the inducible cyclooxygenase-2 gene (PTGS2) with type 2 diabetes mellitus in pima Indians. Hum Genet 113:377–381CrossRefPubMedGoogle Scholar
  48. Ku GM, Kim H, Vaughn IW, Hangauer MJ, Myung Oh C, German MS, McManus MT (2012) Research resource: RNA-Seq reveals unique features of the pancreatic beta-cell transcriptome. Mol Endocrinol 26:1783–1792CrossRefPubMedPubMedCentralGoogle Scholar
  49. Lindskog C, Korsgren O, Ponten F, Eriksson JW, Johansson L, Danielsson A (2012) Novel pancreatic beta cell-specific proteins: antibody-based proteomics for identification of new biomarker candidates. J Proteome 75:2611–2620CrossRefGoogle Scholar
  50. Linnemann AK, Baan M, Davis DB (2014) Pancreatic beta-cell proliferation in obesity. Adv Nutr 5:278–288CrossRefPubMedPubMedCentralGoogle Scholar
  51. Lundstrom K (2009) An overview on GPCRs and drug discovery: structure-based drug design and structural biology on GPCRs. Methods Mol Biol 552:51–66CrossRefPubMedGoogle Scholar
  52. Luo P, Wang MH (2011) Eicosanoids, beta-cell function, and diabetes. Prostaglandins Other Lipid Mediat 95:1–10CrossRefPubMedPubMedCentralGoogle Scholar
  53. Meng ZX, Sun JX, Ling JJ, Lv JH, Zhu DY, Chen Q, Sun YJ, Han X (2006) Prostaglandin E2 regulates Foxo activity via the Akt pathway: implications for pancreatic islet beta cell dysfunction. Diabetologia 49:2959–2968CrossRefPubMedGoogle Scholar
  54. Meng Z, Lv J, Luo Y, Lin Y, Zhu Y, Nie J, Yang T, Sun Y, Han X (2009) Forkhead box O1/pancreatic and duodenal homeobox 1 intracellular translocation is regulated by c-Jun N-terminal kinase and involved in prostaglandin E2-induced pancreatic beta-cell dysfunction. Endocrinology 150:5284–5293CrossRefPubMedGoogle Scholar
  55. Metz SA, Robertson RP, Fujimoto WY (1981) Inhibition of prostaglandin E synthesis augments glucose-induced insulin secretion is cultured pancreas. Diabetes 30:551–557CrossRefPubMedGoogle Scholar
  56. Oshima H, Taketo MM, Oshima M (2006) Destruction of pancreatic beta-cells by transgenic induction of prostaglandin E2 in the islets. J Biol Chem 281:29330–29336CrossRefPubMedGoogle Scholar
  57. Papadimitriou A, King AJ, Jones PM, Persaud SJ (2007) Anti-apoptotic effects of arachidonic acid and prostaglandin E2 in pancreatic beta-cells. Cell Physiol Biochem 20:607–616CrossRefPubMedGoogle Scholar
  58. Parazzoli S, Harmon JS, Vallerie SN, Zhang T, Zhou H, Robertson RP (2012) Cyclooxygenase-2, not microsomal prostaglandin E synthase-1, is the mechanism for interleukin-1beta-induced prostaglandin E2 production and inhibition of insulin secretion in pancreatic islets. J Biol Chem 287:32246–32253CrossRefPubMedPubMedCentralGoogle Scholar
  59. Patrono C, Pugliese F, Ciabattoni G, Di Blasi S, Pierucci A, Cinotti GA, Maseri A, Chierchia S (1981) Prostacyclin does not affect insulin secretion in humans. Prostaglandins 21:379–385CrossRefPubMedGoogle Scholar
  60. Persaud SJ, Burns CJ, Belin VD, Jones PM (2004) Glucose-induced regulation of COX-2 expression in human islets of Langerhans. Diabetes 53(Suppl 1):S190–S192CrossRefPubMedGoogle Scholar
  61. Persaud SJ, Muller D, Belin VD, Papadimitriou A, Huang GC, Amiel SA, Jones PM (2007) Expression and function of cyclooxygenase and lipoxygenase enzymes in human islets of Langerhans. Arch Physiol Biochem 113:104–109CrossRefPubMedGoogle Scholar
  62. Robertson RP (1983) Prostaglandins, glucose homeostasis, and diabetes mellitus. Annu Rev Med 34:1–12CrossRefPubMedGoogle Scholar
  63. Robertson RP (1988) Eicosanoids as pluripotential modulators of pancreatic islet function. Diabetes 37:367–370CrossRefPubMedGoogle Scholar
  64. Robertson RP, Gavareski DJ, Porte D Jr, Bierman EL (1974) Inhibition of in vivo insulin secretion by prostaglandin E1. J Clin Invest 54:310–315CrossRefPubMedPubMedCentralGoogle Scholar
  65. Robertson RP, Tsai P, Little SA, Zhang HJ, Walseth TF (1987) Receptor-mediated adenylate cyclase-coupled mechanism for PGE2 inhibition of insulin secretion in HIT cells. Diabetes 36:1047–1053CrossRefPubMedGoogle Scholar
  66. Sacca L, Perez G, Rengo F, Pascucci I, Condorelli M (1975) Reduction of circulating insulin levels during the infusion of different prostaglandins in the rat. Acta Endocrinol 79:266–274PubMedGoogle Scholar
  67. Sachdeva MM, Stoffers DA (2009) Minireview: meeting the demand for insulin: molecular mechanisms of adaptive postnatal beta-cell mass expansion. Mol Endocrinol 23:747–758CrossRefPubMedPubMedCentralGoogle Scholar
  68. Saisho Y, Butler AE, Manesso E, Elashoff D, Rizza RA, Butler PC (2013) Beta-cell mass and turnover in humans: effects of obesity and aging. Diabetes Care 36:111–117CrossRefPubMedGoogle Scholar
  69. Samad TA, Moore KA, Sapirstein A, Billet S, Allchorne A, Poole S, Bonventre JV, Woolf CJ (2001) Interleukin-1beta-mediated induction of cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature 410:471–475CrossRefPubMedGoogle Scholar
  70. Sanchez-Alavez M, Klein I, Brownell SE, Tabarean IV, Davis CN, Conti B, Bartfai T (2007) Night eating and obesity in the EP3R-deficient mouse. Proc Natl Acad Sci U S A 104:3009–3014CrossRefPubMedPubMedCentralGoogle Scholar
  71. Seaquist ER, Walseth TF, Nelson DM, Robertson RP (1989) Pertussis toxin-sensitive G protein mediation of PGE2 inhibition of cAMP metabolism and phasic glucose-induced insulin secretion in HIT cells. Diabetes 38:1439–1445CrossRefPubMedGoogle Scholar
  72. Shanmugam N, Todorov IT, Nair I, Omori K, Reddy MA, Natarajan R (2006) Increased expression of cyclooxygenase-2 in human pancreatic islets treated with high glucose or ligands of the advanced glycation endproduct-specific receptor (AGER), and in islets from diabetic mice. Diabetologia 49:100–107CrossRefPubMedGoogle Scholar
  73. Shridas P, Zahoor L, Forrest KJ, Layne JD, Webb NR (2014) Group X secretory phospholipase A2 regulates insulin secretion through a cyclooxygenase-2-dependent mechanism. J Biol Chem 289:27410–27417CrossRefPubMedPubMedCentralGoogle Scholar
  74. Sieradzki J, Wolan H, Szczeklik A (1984) Effects of prostacyclin and its stable analog, iloprost, upon insulin secretion in isolated pancreatic islets. Prostaglandins 28:289–296CrossRefPubMedGoogle Scholar
  75. Sjoholm A (1996) Prostaglandins inhibit pancreatic beta-cell replication and long-term insulin secretion by pertussis toxin-insensitive mechanisms but do not mediate the actions of interleukin-1 beta. Biochim Biophys Acta 1313:106–110CrossRefPubMedGoogle Scholar
  76. Sjoholm A, Nystrom T (2006) Inflammation and the etiology of type 2 diabetes. Diabetes Metab Res Rev 22:4–10CrossRefPubMedGoogle Scholar
  77. Sorli CH, Zhang HJ, Armstrong MB, Rajotte RV, Maclouf J, Robertson RP (1998) Basal expression of cyclooxygenase-2 and nuclear factor-interleukin 6 are dominant and coordinately regulated by interleukin 1 in the pancreatic islet. Proc Natl Acad Sci U S A 95:1788–1793CrossRefPubMedPubMedCentralGoogle Scholar
  78. Speroff L, Ramwell PW (1970) Prostaglandin stimulation of in vitro progesterone synthesis. J Clin Endocrinol Metab 30:345–350CrossRefPubMedGoogle Scholar
  79. Szczeklik A, Pieton R, Sieradzki J, Nizankowski R (1980) The effects of prostacyclin on glycemia and insulin release in man. Prostaglandins 19:959–968CrossRefPubMedGoogle Scholar
  80. Tadayyon M, Bonney RC, Green IC (1990) Starvation decreases insulin secretion, prostaglandin E2 production and phospholipase A2 activity in rat pancreatic islets. J Endocrinol 124:455–461CrossRefPubMedGoogle Scholar
  81. Tootle TL (2013) Genetic insights into the in vivo functions of prostaglandin signaling. Int J Biochem Cell Biol 45:1629–1632CrossRefPubMedGoogle Scholar
  82. Tran PO, Gleason CE, Poitout V, Robertson RP (1999) Prostaglandin E(2) mediates inhibition of insulin secretion by interleukin-1beta. J Biol Chem 274:31245–31248CrossRefPubMedGoogle Scholar
  83. Tran PO, Gleason CE, Robertson RP (2002) Inhibition of interleukin-1beta-induced COX-2 and EP3 gene expression by sodium salicylate enhances pancreatic islet beta-cell function. Diabetes 51:1772–1778CrossRefPubMedGoogle Scholar
  84. Vennemann A, Gerstner A, Kern N, Ferreiros Bouzas N, Narumiya S, Maruyama T, Nusing RM (2012) PTGS-2-PTGER2/4 signaling pathway partially protects from diabetogenic toxicity of streptozotocin in mice. Diabetes 61:1879–1887CrossRefPubMedPubMedCentralGoogle Scholar
  85. Wortham M, Sander M (2016) Mechanisms of beta-cell functional adaptation to changes in workload. Diabetes Obes Metab 18(Suppl 1):78–86CrossRefPubMedGoogle Scholar
  86. Yajima M, Hosoda K, Kanbayashi Y, Nakamura T, Nogimori K, Mizushima Y, Nakase Y, Ui M (1978) Islets-activating protein (IAP) in Bordetella pertussis that potentiates insulin secretory responses of rats. Purification and characterization J Biochem 83:295–303PubMedGoogle Scholar
  87. Yasui M, Tamura Y, Minami M, Higuchi S, Fujikawa R, Ikedo T, Nagata M, Arai H, Murayama T, Yokode M (2015) The prostaglandin E2 receptor EP4 regulates obesity-related inflammation and insulin sensitivity. PLoS One 10:e0136304CrossRefPubMedPubMedCentralGoogle Scholar
  88. Yokoyama U, Iwatsubo K, Umemura M, Fujita T, Ishikawa Y (2013) The prostanoid EP4 receptor and its signaling pathway. Pharmacol Rev 65:1010–1052CrossRefPubMedGoogle Scholar
  89. Zawalich WS, Zawalich KC, Yamazaki H (2007) Divergent effects of epinephrine and prostaglandin E2 on glucose-induced insulin secretion from perifused rat islets. Metabolism 56:12–18CrossRefPubMedGoogle Scholar

Copyright information

© The International CCN Society (outside the USA) 2017

Authors and Affiliations

  • Bethany A. Carboneau
    • 1
    • 2
    • 3
  • Richard M. Breyer
    • 1
    • 4
  • Maureen Gannon
    • 1
    • 2
    • 3
    • 5
    • 6
  1. 1.Department of Veterans Affairs, Tennessee Valley Health AuthorityNashvilleUSA
  2. 2.Department of Molecular Physiology and BiophysicsVanderbilt UniversityNashvilleUSA
  3. 3.Program in Developmental BiologyVanderbilt UniversityNashvilleUSA
  4. 4.Department of Medicine, Division of NephrologyVanderbilt University Medical CenterNashvilleUSA
  5. 5.Department of Cell and Developmental BiologyVanderbilt UniversityNashvilleUSA
  6. 6.Department of Medicine, Division of Diabetes, Endocrinology and MetabolismVanderbilt University Medical CenterNashvilleUSA

Personalised recommendations