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2014 | 61 | 4 | 655-662
Article title

Purinergic signaling in the pancreas and the therapeutic potential of ecto-nucleotidases in diabetes

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EN
Abstracts
EN
It is widely accepted that purinergic signaling is involved in the regulation of functions of all known tissues and organs. Extracellular purines activate two classes of receptors, P1-adenosine receptors and P2-nucleotide receptors, in a concentration-dependent manner. Ecto-enzymes metabolizing nucleotides outside the cell are involved in the termination of the nucleotide signaling pathway through the release of ligands from their receptors. The pancreas is a central organ in nutrient and energy homeostasis with endocrine, exocrine and immunoreactive functions. The disturbances in cellular metabolism in diabetes mellitus lead also to changes in concentrations of intra- and extracellular nucleotides. Purinergic receptors P1 and P2 are present on the pancreatic islet cells as well as on hepatocytes, adipocytes, pancreatic blood vessels and nerves. The ATP-dependent P2X receptor activation on pancreatic β-cells results in a positive autocrine signal and subsequent insulin secretion. Ecto-NTPDases play the key role in regulation of extracellular ATP concentration. These enzymes, in cooperation with 5'-nucleotidase can significantly increase ecto-adenosine concentration. It has been demonstrated that adenosine, through activation of P1 receptors present on adipocytes and pancreatic islets cells, inhibits the release of insulin. Even though we know for 50 years about the regulatory role of nucleotides in the secretion of insulin, an integrated understanding of the involvement of purinergic signaling in pancreas function is still required. This comprehensive review presents our current knowledge about purinergic signaling in physiology and pathology of the pancreas as well as its potential therapeutic relevance in diabetes.
Publisher

Year
Volume
61
Issue
4
Pages
655-662
Physical description
Dates
published
2014
received
2014-02-25
revised
2014-05-26
accepted
2014-12-12
(unknown)
2014-12-19
Contributors
  • Neurology Department, Regional Polyclinical Hospital in Toruń, Toruń, Poland
  • Department of Biochemistry, Faculty of Biology and Environment Protection, Nicolaus Copernicus University in Toruń, Toruń, Poland
References
  • Amisten S, Meidute-Abaraviciene S, Tan C, Olde B, Lundquist I, Salehi A, Erlinge D (2010) ADP mediates inhibition of insulin secretion by activation of P2Y13 receptors in mice. Diabetologia 53: 1927-1934.
  • Bertrand G, Chapal J, Loubatieres-Mariani MM (1986) Potentiating synergism between adenosine diphosphate or triphosphate and acetylcholine on insulin secretion. Am J Physiol 251: E416-E421.
  • Böck P (1989) Fate of ATP in secretory granules: phosphohydrolase studies in pancreatic vascular bed. Arch Histol Cytol 52: 85-90.
  • Budohoski L, Challiss RA, Cooney GJ, McManus B, Newsholme EA (1984) Reversal of dietary-induced insulin resistance in muscle of the rat by adenosine deaminase and an adenosine-receptor antagonist. Biochem J 224: 327-330.
  • Burnstock G, Novak I (2013) Purinergic signalling and diabetes. Purinergic Signal 9: 307-324.
  • Burnstock G, Novak I (2012) Purinergic signalling in the pancreas in health and disease. J Endocrinol 213: 123-141.
  • Burnstock G (2013) Purinergic signalling in endocrine organs. Purinergic Signal 10: 189-231.
  • Carlson LA (2005) Nicotinic acid: the broad-spectrum lipid drug. A 50th anniversary review. J Intern Med 258: 94-114.
  • Challis RA, Budohoski L, McManus B, Newsholme EA (1984) Effects of an adenosine-receptor antagonist on insulin-resistance in soleus muscle from obese Zucker rats. Biochem J 221: 915-917.
  • Chapal J, Bertrand G, Hillaire-Buys D, Gross R, Loubatières-Mariani MM (1993) Prior glucose deprivation increases the first phase of glucose-induced insulin response: possible involvement of endogenous ATP and (or) ADP. Can J Physiol Pharmacol 71: 611-614.
  • Chapal J, Loubatières-Mariani MM, Petit P, Roye M (1985) Evidence for an A2-subtype adenosine receptor on pancreatic glucagon secreting cells. Br J Pharmacol 86: 565-569.
  • Cheng JT, Chi TC, Liu IM (2000) Activation of adenosine A1 receptors by drugs to lower plasma glucose in streptozotocin-induced diabetic rats. Auton Neurosci 83: 127-133.
  • Chia JS, McRae JL, Cowan PJ, Dwyer KM (2012) The CD39-adenosinergic axis in the pathogenesis of immune and nonimmune diabetes. J Biomed Biotechnol 2012: 320495.
  • Cieślak M (2012) Role of purinergic signalling and cytokines in the ischaemic stroke. Aktualności Neurol 12: 205-214 (in Polish).
  • Cieślak M, Komoszyński M (2004) Role and potential therapeutic importance of nucleotides and nucleosides in the ischaemic stroke. Aktualności Neurol 4: 126-131 (in Polish).
  • Crack B E, Pollard CE, Beukers M W, Roberts SM, Hunt SF, Ingall AH, McKechnie KC, IJzerman AP, Leff P (1995) Pharmacological and biochemical analysis of FPL 67156, a novel, selective inhibitor of ecto-ATPase. Br J Pharmacol 114: 475-481.
  • Csóka B, Koscsó B, Töro G, Kókai E, Virág L, Németh ZH, Pacher P, Bai P, Haskó G (2014) A2B adenosine receptors prevent insulin resistance by inhibiting adipose tissue inflammation via maintaining alternative macrophage activation. Diabetes 63: 850-866.
  • Dhalla AK, Chisholm JW, Reaven GM, Belardinelli L (2009) A1 adenosine receptor: role in diabetes and obesity. Handb Exp Pharmacol 193: 271-295.
  • Dole VP (1961) Effect of nucleic acid metabolites on lipolysis in adipose tissue. J Biol Chem 236: 3125-3130.
  • Drews G, Krippeit-Drews P, Düfer M (2010) Electrophysiology of islet cells. Adv Exp Med Biol 654: 115-163.
  • Fain JN, Pointer RH, Ward WF (1972) Effects of adenosine nucleosides on adenylate cyclase, phosphodiesterase, cyclic adenosine monophosphate accumulation, and lipolysis in fat cells. J Biol Chem 247: 6866-6872.
  • Fernandez-Alvarez J, Hillaire-Buys D, Loubatières-Mariani MM, Gomis R, Petit P (2001) P2 receptor agonists stimulate insulin release from human pancreatic islets. Pancreas 22: 69-71.
  • Figler RA, Wang G, Srinivasan S, Jung DY, Zhang Z, Pankow JS, Ravid K, Fredholm B, Hedrick CC, Rich SS, Kim JK, LaNoue KF, Linden J (2011) Links between insulin resistance, adenosine A2B receptors, and inflammatory markers in mice and humans. Diabetes 60: 669-679.
  • Fong P, Argent BE, Guggino WB, Gray MA (2003) Characterization of vectorial chloride transport pathways in the human pancreatic duct adenocarcinoma cell line HPAF. Am J Physiol Cell Physiol 285: C433-445.
  • Fredholm BB, IJzerman AP, Jacobson KA, Linden J, Müller CE (2011) International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and classification of adenosine receptors - an update. Pharmacol Rev 63: 1-34.
  • Han DH, Hansen PA, Nolte LA, Holloszy JO (1998) Removal of adenosine decreases the responsiveness of muscle glucose transport to insulin and contractions. Diabetes 47: 1671-1675.
  • Hennigs JK, Seiz O, Spiro J, Berna MJ, Baumann HJ, Klose H, Pace A (2011) Molecular basis of P2-receptor-mediated calcium signaling in activated pancreatic stellate cells. Pancreas 40: 740-746.
  • Ismail NA, El Denshary EE, Montague W (1977) Adenosine and the regulation of insulin secretion by isolated rat islets of Langerhans. Biochem J 164: 409-413.
  • Jacques-Silva MC, Cabrera O, Makeeva N, Berman D, Kenyon NS, Ricordi C, Pileggi A, Molano RD, Berggren PO, Caicedo A (2008) Endogenously released ATP serves as a positive autocrine feedback loop for the human pancreatic beta cell. Purinergic Signal 4: S49.
  • Jacques-Silva M C, Correa-Medina M, Cabrera O, Rodriguez-Diaz R, Makeeva N, Fachado A, Diez J, Berman DM, Kenyon NS, Ricordi C, Pileggi A, Molano RD, Berggren PO, Caicedo A (2010) ATP-gated P2X3 receptors constitute a positive autocrine signal for insulin release in the human pancreatic beta cell. Proc Natl Acad Sci USA 107: 6465-6470.
  • Johansson SM, Salehi A, Sandström ME, Westerblad H, Lundquist I, Carlsson PO, Fredholm BB, Katz A (2007) A1 receptor deficiency causes increased insulin and glucagon secretion in mice. Biochem Pharmacol 74: 1628-1635.
  • Kado S, Nagase T, Nagata N (1999) Circulating levels of interleukin-6, its soluble receptor and interleukin-6/interleukin-6 receptor complexes in patients with type 2 diabetes mellitus. Acta Diabetol 36: 67-72.
  • Karanauskaite J, Hoppa MB, Braun M, Galvanovskis J, Rorsman P (2009) Quantal ATP release in rat beta-cells by exocytosis of insulin-containing LDCVs. Pflugers Arch 458: 389-401.
  • Kittel A, Garrido M, Varga G (2002) Localization of NTPDase1/CD39 in normal and transformed human pancreas. J Histochem Cytochem 50: 549-556.
  • Künzli BM, Berberat PO, Giese T, Csizmadia E, Kaczmarek E, Baker C, Halaceli I, Büchler MW, Friess H, Robson SC (2007) Upregulation of CD39/NTPDases and P2 receptors in human pancreatic disease. Am J Physiol Gastrointest Liver Physiol 292: G223-G230.
  • Kuroda M, Honnor RC, Cushman SW, Londos C, Simpson IA (1987) Regulation of insulin-stimulated glucose transport in the isolated rat adipocyte. cAMP-independent effects of lipolytic and antilipolytic agents. J Biol Chem 262: 245-253.
  • Lavoie EG, Fausther M, Kauffenstein G, Kukulski F, Künzli BM, Friess H, Sévigny J (2010) Identification of the ectonucleotidases expressed in mouse, rat, and human Langerhans islets: potential role of NTPDase3 in insulin secretion. Am J Physiol Endocrinol Metab 299: E647-E656.
  • Lazarowski ER (2012) Vesicular and conductive mechanisms of nucleotide release. Purinergic Signal 8: 359-373.
  • Leitner JW, Sussman KE, Vatter AE, Schneider FH (1975) Adenine nucleotides in the secretory granule fraction of rat islets. Endocrinology 96: 662-677.
  • Léon C, Freund M, Latchoumanin O, Farret A, Petit P, Cazenave JP, Gachet C (2005) The P2Y(1) receptor is involved in the maintenance of glucose homeostasis and in insulin secretion in mice. Purinergic Signal 1: 145-151.
  • Lévesque SA, Lavoie EG, Lecka J, Bigonnesse F, Sévigny J (2007) Specificity of the ecto-ATPase inhibitor ARL 67156 on human and mouse ectonucleotidases. Br J Pharmacol 152: 141-150.
  • Linden J (2006) New insights into the regulation of inflammation by adenosine. J Clin Invest 116: 1835-1837.
  • Loubatières-Mariani MM, Loubatières AL, Chapal J, Valette G (1976) Adenosine triphosphate (ATP) and glucose. Action on insulin and glucagon secretion. C R Seances Soc Biol Fil 170: 833-836.
  • Lugo-Garcia L, Nadal B, Gomis R, Petit P, Gross R, Lajoix AD (2008) Human pancreatic islets express the purinergic P2Y11 and P2Y12 receptors. Horm Metab Res 40: 827-830.
  • Lunkes GI, Lunkes D, Stefanello F, Morsch A, Morsch VM, Mazzanti CM, Schetinger MR (2003) Enzymes that hydrolyze adenine nucleotides in diabetes and associated pathologies. Thromb Res 109: 189-194.
  • Ma LJ, Mao S L, Taylor KL, Kanjanabuch T, Guan Y, Zhang Y, Brown NJ, Swift LL, McGuinness OP, Wasserman DH, Vaughan DE, Fogo AB (2004) Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1. Diabetes 53: 336-346.
  • Munkonda MN, Pelletier J, Ivanenkov VV, Fausther M, Tremblay A, Künzli B, Kirley TL, Sévigny J (2009) Characterization of a monoclonal antibody as the first specific inhibitor of human NTP diphosphohydrolase-3: partial characterization of the inhibitory epitope and potential applications . FEBS J 276: 479-496.
  • Nieto-Vazquez I, Fernández-Veledo S, de Alvaro C, Lorenzo M (2008) Dual role of interleukin-6 in regulating insulin sensitivity in murine skeletal muscle. Diabetes 57: 3211-3221.
  • Novak I (2008) Purinergic receptors in the endocrine and exocrine pancreas. Purinergic Signal 4: 237-253.
  • Ohtani M, Suzuki J, Jacobson KA, Oka T (2008) Evidence for the possible involvement of the P2Y(6) receptor in Ca(2+) mobilization and insulin secretion in mouse pancreatic islets. Purinergic Signal 4: 365-375.
  • Parandeh F, Abaraviciene SM, Amisten S, Erlinge D, Salehi A (2008) Uridine diphosphate (UDP) stimulates insulin secretion by activation of P2Y6 receptors. Biochem Biophys Res Commun 370: 499-503.
  • Petit P, Hillaire-Buys D, Manteghetti M, Debrus S, Chapal J, Loubatières-Mariani MM (1998) Evidence for two different types of P2 receptors stimulating insulin secretion from pancreatic beta cell. Br J Pharmacol 125: 1368-1374.
  • Petit P, Lajoix AD, Gross R (2009) P2 purinergic signalling in the pancreatic beta-cell: control of insulin secretion and pharmacology. Eur J Pharm Sci 37: 67-75.
  • Poynten AM, Gan SK, Kriketos AD, O'Sullivan A, Kelly JJ, Ellis BA, Chisholm DJ, Campbell LV (2003) Nicotinic acid-induced insulin resistance is related to increased circulating fatty acids and fat oxidation but not muscle lipid content. Metabolism 52: 699-704.
  • Robson SC, Sévigny J, Zimmermann H (2006) The E-NTPDase family of ectonucleotidases: structure, function, relationships and pathophysiological significance. Purinergic Signal 2: 409-430.
  • Rodrigue-Candela J, Martin-Hernandez D, Castilla-Cortazar T (1963) Stimulation of insulin secretion in vitro by adenosine triphosphate. Nature 197: 1304.
  • Rüsing D, Müller CE, Verspohl EJ (2006) The impact of adenosine and A(2B) receptors on glucose homoeostasis. J Pharm Pharmacol 58: 1639-1645.
  • Ryzhov S, Zaynagetdinov R, Goldstein AE, Novitskiy SV, Dikov MM, Blackburn MR, Biaggioni I, Feoktistov I (2008) Effect of A2B adenosine receptor gene ablation on proinflammatory adenosine signaling in mast cells. J Immunol 180: 7212-7220.
  • Salehi A, Parandeh F, Fredholm BB, Grapengiesser E, Hellman B (2009) Absence of adenosine A1 receptors unmasks pulses of insulin release and prolongs those of glucagon and somatostatin. Life Sci 85: 470-476.
  • Santini E, Cuccato S, Madec S, Chimenti D, Ferrannini E, Solini A (2009) Extracellular adenosine 5'-triphosphate modulates insulin secretion via functionally active purinergic receptors of X and Y subtype. Endocrinology 150: 2596-2602.
  • Sarvas JL, Khaper N, Lees SJ (2013) The IL-6 Paradox: Context Dependent Interplay of SOCS3 and AMPK. J Diabetes Metab Suppl 13.
  • Schwabe U, Ebert R, Erbler HC (1973) Adenosine release from isolated fat cells and its significance for the effects of hormones on cyclic 3',5'-AMP levels and lipolysis. Naunyn Schmiedebergs Arch Pharmacol 276: 133-148.
  • Schwabe U, Ebert R (1974) Stimulation of cyclic adenosine 3',5'-monophosphate accumulation and lipolysis in fat cells by adenosine deaminase. Naunyn Schmiedebergs Arch Pharmacol 282: 33--44.
  • Silva AM, Rodrigues RJ, Tomé AR, Cunha RA, Misler S, Rosário LM, Santos RM (2008) Electrophysiological and immunocytochemical evidence for P2X purinergic receptors in pancreatic beta cells. Pancreas 36: 279-283.
  • Sochocka M (2008) Rozpoznawanie patogenów przez wrodzony system odporności. Postepy Hig Med Dosw 62: 676-687 (in Polish).
  • Squires PE, James RF, London NJ, Dunne MJ (1994) ATP-induced intracellular Ca2+ signals in isolated human insulin-secreting cells. Pflugers Arch 427: 181-183.
  • Stagner JI, Samols E (1985) Role of intrapancreatic ganglia in regulation of periodic insular secretions. Am J Physiol 248: E522-E530.
  • Stam NJ, Klomp J, Van de Heuvel N, Olijve W (1996) Molecular cloning and characterization of a novel orphan receptor (P2P) expressed in human pancreas that shows high structural homology to the P2U purinoceptor. FEBS Lett 384: 260-264.
  • Tahani HM (1979) The purinergic nerve hypothesis and insulin secretion. Z Ernahrungswiss 18: 128-138.
  • Thompson LF, Eltzschig HK, Ibla JC, Van De Wiele CJ, Resta R, Morote-Garcia JC, Colgan SP (2004) Crucial role for ecto-5'-nucleotidase (CD73) in vascular leakage during hypoxia. J Exp Med 200: 1395-1405.
  • Töpfer M, Burbiel CE, Müller CE, Knittel J, Verspohl EJ (2008) Modulation of insulin release by adenosine A1 receptor agonists and antagonists in INS-1 cells: the possible contribution of 86Rb+ efflux and 45Ca2+ uptake. Cell Biochem Funct 26: 833-843.
  • Tuduri E, Filiputti E, Carneiro EM, Quesada I (2008) Inhibition of Ca2+ signaling and glucagon secretion in mouse pancreatic alpha-cells by extracellular ATP and purinergic receptors. Am J Physiol Endocrinol Metab 294: E952-E960.
  • Verspohl EJ, Johannwille B, Waheed A, Neye H (2002) Effect of purinergic agonists and antagonists on insulin secretion from INS-1 cells (insulinoma cell line) and rat pancreatic islets. Can J Physiol Pharmacol 80: 562-568.
  • Wang C, Geng B, Cui Q, Guan Y, Yang J (2014) Intracellular and extracellular adenosine triphosphate in regulation of insulin secretion from pancreatic β cells. J Diabetes 6: 113-119.
  • Weir GC, Knowlton SD, Martin DB (1975) Nucleotide and nucleoside stimulation of glucagon secretion. Endocrinology 97: 932-936.
  • Westfall TD, Kennedy C, Sneddon P (1997) The ecto-ATPase inhibitor ARL 67156 enhances parasympathetic neurotransmission in the guinea-pig urinary bladder. Eur J Pharmacol 329: 169-173.
  • Yang GK, Fredholm BB, Kieffer TJ, Kwok YN (2012) Improved blood glucose disposal and altered insulin secretion patterns in adenosine A(1) receptor knockout mice. Am J Physiol Endocrinol Metab 303: E180-E190.
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Publication order reference
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YADDA identifier
bwmeta1.element.bwnjournal-article-abpv61p655kz
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