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Regulators of Beta-Cell Death and Regeneration

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Book cover Pancreatic Islet Biology

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

Pancreatic β-cell deficiency underlies both type 1 and type 2 diabetes, and restoration or replacement of β-cell mass/function is therefore the logical long-term solution to therapy. While it has long been held that type 1 diabetes results from an irreversible loss of β-cells, and that type 2 diabetes is primarily caused by impaired insulin action, there is now increasing evidence linking both types of diabetes to defects in β-cell mass and insulin secretion. Pancreatic β-cells have traditionally been viewed as a quiescent cell population. However, several recent lines of evidence indicated that like most tissues the β-cell mass is dramatically regulated with ongoing β-cell regeneration throughout life to replenish lost or damaged β-cells. Based on our recent data concerning β-cell death , dysfunction, and regeneration , we would like to describe regulation of pancreatic β-cell death, functioning, and regeneration.

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References

  • Abdel-Wahab MH, Abd-Allah AR (2000) Possible protective effect of melatonin and/or desferrioxamine against streptozotocin-induced hyperglycaemia in mice. Pharmacol Res 41(5):533–537

    Article  CAS  PubMed  Google Scholar 

  • Abe M, Nata K, Akiyama T, Shervani NJ, Kobayashi S, Tomioka-Kumagai T, Ito S, Takasawa S, Okamoto H (2000) Identification of a novel Reg family gene, Reg IIIδ, and mapping of all three types of Reg family gene in a 75 kilobase mouse genomic region. Gene 246(102):111–122

    Article  CAS  PubMed  Google Scholar 

  • Aida K, Saitoh S, Nishida Y, Yokota S, Ohno S, Mao X, Akiyama D, Tanaka S, Awata T, Shimada A, Oikawa Y, Shimura H, Furuya F, Takizawa S, Ichijo M, Ichijo S, Itakura J, Fujii H, Hashiguchi A, Takasawa S, Endo T, Kobayashi T (2014) Distinct cell clusters touching islet cells induce islet cell replication in association with over-expression of regenerating gene (REG) protein in fulminant Type 1 diabetes. PLoS ONE 9(4):e95110

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Akabane A, Kato I, Takasawa S, Unno M, Yonekura H, Yoshimoto T, Okamoto H (1995) Nicotinamide inhibits IRF-1 mRNA induction and prevents IL-1β-induced nitric oxide synthase expression in pancreatic β-cells. Biochem Biophys Res Commun 215(2):524–530

    Article  CAS  PubMed  Google Scholar 

  • Akiyama T, Takasawa S, Nata K, Kobayashi S, Abe M, Shervani NJ, Ikeda T, Nakagawa K, Unno M, Matsuno S, Okamoto H (2001) Activation of Reg gene, a gene for insulin-producing β-cell regeneration: poly(ADP-ribose) polymerase binds Reg promoter and regulates the transcription by autopoly(ADP-ribosyl)ation. Proc Natl Acad Sci USA 98(1):48–53

    CAS  PubMed  Google Scholar 

  • Alano CC, Garnier P, Ying W, Higashi Y, Kauppinen TM, Swanson RA (2010) NAD+ depletion is necessary and sufficient for poly(ADP-ribose) polymerase-1-mediated neuronal death. J Neurosci 30(8):2967–2978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • An NH, Han MK, Um C, Park BH, Park BJ, Kim HK, Kim UH (2001) Significance of ecto-cyclase activity of CD38 in insulin secretion of mouse pancreatic islet cells. Biochem Biophys Res Commun 282(3):781–786

    Article  CAS  PubMed  Google Scholar 

  • Andrabi SA, Dawson TM, Dawson VL (2008) Mitochondrial and nuclear cross talk in cell death: parthanatos. Ann NY Acad Sci 1147:233–241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Antonelli A, Baj G, Marchetti P, Fallahi P, Surico N, Pupilli C, Malavasi F, Ferrannini E (2001) Human anti-CD38 autoantibodies raise intracellular calcium and stimulate insulin release in human pancreatic islets. Diabetes 50(5):985–991

    Article  CAS  PubMed  Google Scholar 

  • Antonelli A, Tuomi T, Nannipieri M, Fallahi P, Nesti C, Okamoto H, Groop L, Ferrannini E (2002) Autoimmunity to CD38 and GAD in Type I and Type II diabetes: CD38 and HLA genotypes and clinical phenotypes. Diabetologia 45(9):1298–12306

    Article  CAS  PubMed  Google Scholar 

  • Ashcroft FM, Harrison DE, Ashcroft SJH (1984) Glucose induces closure of single potassium channels in isolated rat pancreatic β-cells. Nature 312(5993):446–448

    Article  CAS  PubMed  Google Scholar 

  • Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA (1922) Pancreatic extracts in the treatment of diabetes mellitus: preliminary report. Can Med Assoc J 12:141–146

    CAS  PubMed  PubMed Central  Google Scholar 

  • Berridge MJ, Irvine RF (1984) Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 312(5992):315–321

    Article  CAS  PubMed  Google Scholar 

  • Bonner-Weir S (2000) Perspective: postnatal pancreatic β-cell growth. Endocrinology 141(6):1926–1929

    CAS  PubMed  Google Scholar 

  • Bowes J, McDonald MC, Piper J, Thiemermann C (1999) Inhibitors of poly (ADP-ribose) synthetase protect rat cardiomyocytes against oxidant stress. Cardiovasc Res 41(1):126–134

    Article  CAS  PubMed  Google Scholar 

  • Burkart V, Wang Z-Q, Radons J, Heller B, Herceg Z, Stingl L, Wagner EF, Kolb H (1999) Mice lacking the poly(ADP-ribose) polymerase gene are resistant to pancreatic beta-cell destruction and diabetes development induced by streptozocin. Nature Med 5(3):314–319

    Article  CAS  PubMed  Google Scholar 

  • Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC (2003) β-Cell deficit and increased β-cell apoptosis in humans with Type 2 diabetes. Diabetes 52(1):102–110

    Article  CAS  PubMed  Google Scholar 

  • Calderari S, Irminger J-C, Giroix M-H, Ehses JA, Gangnerau M-N, Coulaud J, Rickenbach K, Gauguier D, Halban P, Serradas P, Homo-Delarche F (2014) Regenerating 1 and 3b gene expression in the pancreas of type 2 diabetic Goto-Kakizaki (GK) rats. PLoS ONE 9(2):e90045

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cetkovic-Cvrlje M, Eizirik DL (1994) TNF-α and IFN-γ potentiate the deleterious effects of IL-1β on mouse pancreatic islets mainly via generation of nitric oxide. Cytokine 6(4):399–406

    Article  CAS  PubMed  Google Scholar 

  • Chambon P, Weill JD, Doly J, Strosser MT, Mandel P (1966) On the formation of a novel adenylic compound by enzymatic extracts of liver nuclei. Biochem Biophys Res Commun 25(6):638–643

    Article  CAS  Google Scholar 

  • Charron MJ, Bonner-Weir S (1999) Implicating PARP and NAD+ depletion in type I diabetes. Nature Med 5(3):269–270

    Article  CAS  PubMed  Google Scholar 

  • Clapper DL, Walseth TF, Dargie PJ, Lee HC (1987) Pyridine nucleotide metabolites stimulate calcium release from sea urchin egg microsomes desensitized to inositol trisphosphate. J Biol Chem 262(20):9561–9568

    CAS  PubMed  Google Scholar 

  • Cocco RE, Ucker DS (2001) Distinct modes of macrophage recognition for apoptotic and necrotic cells are not specified exclusively by phosphatidylserine exposure. Mol Biol Cell 12(4):919–930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Concannon P, Rich SS, Nepom GT (2009) Genetics of type 1A diabetes. N Engl J Med 360(16):1646–1654

    Article  CAS  PubMed  Google Scholar 

  • Cooperstein SJ, Watkins D (1981) Actions of toxic drugs on islet cells. In: Cooperstein SJ, Watkins D (eds) The islets of Langerhans. Academic Press, New York, pp 387–425

    Google Scholar 

  • D’Aleo V, Del Guerra S, Martano M, Bonamassa B, Canistro D, Soleti A, Valgimigli L, Paolini M, Filipponi F, Boggi U, Del Prato S, Lupi R (2009) The non-peptidyl low molecular weight radical scavenger IAC protects human pancreatic islets from lipotoxicity. Mol Cell Endocrinol 309(1–2):63–66

    Article  PubMed  CAS  Google Scholar 

  • del Moral RM, Gómez-Morales M, Hernández-Cortés P, Aguilar D, Caballero T, Aneiros-Fernández J, Caba-Molina M, Rodríguez-Martínez MD, Peralta A, Galindo-Moreno P, Osuna A, Oliver FJ, del Moral RG, O’Valle F (2013) PARP inhibition attenuates histopathological lesion in ischemia/reperfusion renal mouse model after cold prolonged ischemia. Sci World J 2013:486574

    Google Scholar 

  • Ducrocq S, Benjelloun N, Plotkine M, Ben-Ari Y, Charriaut-Marlangue C (2000) Poly(ADP-ribose) synthase inhibition reduces ischemic injury and inflammation in neonatal rat brain. J Neurochem 74(6):2504–2511

    Article  CAS  PubMed  Google Scholar 

  • Dunn JS, Sheehan HL, McLetchie NGB (1943) Necrosis of islets of Langerhans produced experimentally. Lancet 241(6242):484–487

    Article  Google Scholar 

  • Dusetti NJ, Frigerio JM, Fox MF, Swallow DM, Dagorn JC, Iovanna JL (1994) Molecular cloning, genomic organization, and chromosomal localization of the human pancreatitis-associated protein (PAP) gene. Genomics 19(1):108–114

    Article  CAS  PubMed  Google Scholar 

  • Ebihara S, Sasaki T, Hida W, Kikuchi Y, Oshiro T, Shimura S, Takasawa S, Okamoto H, Nishiyama A, Akaike N, Shirato K (1997) Role of cyclic ADP-ribose in ATP-activated potassium currents in alveolar macrophages. J Biol Chem 272(25):16026–16029

    Article  Google Scholar 

  • Eliasson MJ, Sampei K, Mandir AS, Hurn PD, Traystman RJ, Bao J, Pieper A, Wang ZQ, Dawson TM, Snyder SH, Dawson VL (1997) Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia. Nat Med 3(10):1089–1095

    Article  CAS  PubMed  Google Scholar 

  • Erickson LC, Bradley MO, Kohn KW (1977) Strand breaks in DNA from normal and transformed human cells treated with 1,3-bis(2-chloroethyl)-1-nitrosourea. Cancer Res 37(10):3744–3750

    CAS  PubMed  Google Scholar 

  • Florez JC (2008) Newly identified loci highlight beta cell dysfunction as a key cause of type 2 diabetes: where are the insulin resistance genes? Diabetologia 51(7):1100–1110

    Article  CAS  PubMed  Google Scholar 

  • Fukui H, Kinoshita Y, Maekawa T, Okada A, Waki S, Hassan S, Okamoto H, Chiba T (1998) Regenerating gene protein may mediate gastric mucosal proliferation induced by hypergastrinemia in rats. Gastroenterology 115(6):1483–1493

    Article  CAS  PubMed  Google Scholar 

  • Gale EA (1996) Molecular mechanisms of beta-cell destruction in IDDM: the role of nicotinamide. Horm Res 45(suppl 1):39–43

    PubMed  Google Scholar 

  • Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, Dawson TM, Dawson VL, El-Deiry WS, Fulda S, Gottlieb E, Green DR, Hengartner MO, Kepp O, Knight RA, Kumar S, Lipton SA, Lu X, Madeo F, Malorni W, Mehlen P, Nuñez G, Peter ME, Piacentini M, Rubinsztein DC, Shi Y, Simon HU, Vandenabeele P, White E, Yuan J, Zhivotovsky B, Melino G, Kroemer G (2012) Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ 19(1):107–120

    Article  CAS  PubMed  Google Scholar 

  • Giannone PJ, Alcamo AA, Schanbacher BL, Nankervis CA, Besner GE, Bauer JA (2011) Poly(ADP-ribose) polymerase-1: a novel therapeutic target in necrotizing enterocolitis. Pediatr Res 70(1):67–71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goto Y, Kakizaki M, Masaki N (1976) Production of spontaneous diabetic rats by repetition of selective breeding. Tohoku J Exp Med 119(1):85–90

    Article  CAS  PubMed  Google Scholar 

  • Gross DJ, Weiss L, Reibstein I, van den Brand J, Okamoto H, Clark A, Slavin S (1998) Amelioration of diabetes in nonobese diabetic mice with advanced disease by linomide-induced immunoregulation combined with Reg protein treatment. Endocrinology 139(5):2369–2374

    CAS  PubMed  Google Scholar 

  • Gunton JE, Kulkarni RN, Yim S, Okada T, Hawthorne WJ, Tseng YH, Roberson RS, Ricordi C, O’Connell PJ, Gonzalez FJ, Kahn CR (2005) Loss of ARNT/HIF1β mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetes. Cell 122:337–349

    Article  CAS  PubMed  Google Scholar 

  • Haber F, Weiss J (1934) The catalytic decomposition of hydrogen peroxide by iron salts. Proc R Soc Lond A147:332–351

    Article  Google Scholar 

  • Hammarström L, Ullberg S (1966) Specific uptake of labeled alloxan in the pancreatic islets. Nature 212:708–709

    Article  Google Scholar 

  • Hans CP, Feng Y, Naura AS, Zerfaoui M, Rezk BM, Xia H, Kaye AD, Matrougui K, Lazartigues E, Boulares AH (2009) Protective effects of PARP-1 knockout on dyslipidemia-induced autonomic and vascular dysfunction in ApoE mice: effects on eNOS and oxidative stress. PLoS ONE 4(10):e7430

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Harraz MM, Dawson TM, Dawson VL (2008) Advances in neuronal cell death 2007. Stroke 39(2):286–288

    Article  PubMed  Google Scholar 

  • Hartupee JC, Zhang H, Bonaldo MF, Soares MB, Dieckgaefe BK (2001) Isolation and characterization of a cDNA encoding a novel member of the human regenerating protein family: Reg IV. Biochim Biophys Acta 1518(3):287–293

    Article  CAS  PubMed  Google Scholar 

  • Havranek T, Aujla PK, Nickola TJ, Rose MC, Scavo LM (2010) Increased poly(ADP-ribose) polymerase (PARP)-1 expression and activity are associated with inflammation but not goblet cell metaplasia in murine models of allergen-induced airway inflammation. Exp Lung Res 36(7):381–389

    Article  CAS  PubMed  Google Scholar 

  • Heikkila RE, Winston B, Cohen G, Barden H (1976) Alloxan-induced diabetes—evidence for hydroxyl radical as a cytotoxic intermediate. Biochem Pharmacol 25(9):1085–1092

    Article  CAS  PubMed  Google Scholar 

  • Hellerström C, Swenne I (1991) Functional maturation and proliferation of fetal pancreatic β-cells. Diabetes 40(Suppl. 2):89–93

    Article  PubMed  Google Scholar 

  • Hoorens A, Pipeleers D (1999) Nicotinamide protects human beta cells against chemically-induced necrosis, but not against cytokine-induced apoptosis. Diabetologia 42(1):55–59

    Article  CAS  PubMed  Google Scholar 

  • Howard M, Grimaldi JC, Bazan JF, Lund FE, Santos-Argumedo L, Parkhouse RM, Walseth TF, Lee HC (1993) Formation and hydrolysis of cyclic ADP-ribose catalyzed by lymphocyte antigen CD38. Science 262(5136):1056–1059

    Google Scholar 

  • Hua SY, Tokimasa T, Takasawa S, Furuya Y, Nohmi M, Okamoto H, Kuba K (1994) Cyclic ADP-ribose modulates Ca2+ release channels for activation by physiological Ca2+ entry in bullfrog sympathetic neurons. Neuron 12(5):1073–1079

    Article  CAS  PubMed  Google Scholar 

  • Ikehata F, Satoh J, Nata K, Tohgo A, Nakazawa T, Kato I, Kobayashi S, Akiyama T, Takasawa S, Toyota T, Okamoto H (1998) Autoantibodies against CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) that impair glucose-induced insulin secretion in noninsulin-dependent diabetes patients. J Clin Invest 102(2):395–401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Islam MS, Berggren PO (1997) Cyclic ADP-ribose and the pancreatic beta cell: where do we stand? Diabetologia 40(12):1480–1484

    Article  CAS  PubMed  Google Scholar 

  • Islam MS, Larsson O, Berggren PO (1993) Cyclic ADP-ribose in β-cells. Science 262(5133):584–586

    Article  CAS  PubMed  Google Scholar 

  • Jacobson MD, Weil M, Raff MC (1997) Programmed cell death in animal development. Cell 88(3):347–354

    Article  CAS  PubMed  Google Scholar 

  • Jijon HB, Churchill T, Malfair D, Wessler A, Jewell LD, Parsons HG, Madsen KL (2000) Inhibition of poly(ADP-ribose) polymerase attenuates inflammation in a model of chronic colitis. Am J Physiol Gastrointest Liver Physiol 279(3):G641–G651

    CAS  PubMed  Google Scholar 

  • Jörns A, Munday R, Tiedge M, Lenzen S (1997) Comparative toxicity of alloxan, N-alkylalloxans and ninhydrin to isolated pancreatic islets in vitro. J Endocrinol 155(2):283–293

    Article  PubMed  Google Scholar 

  • Kämäräinen M, Heiskala K, Knuutila S, Heiskala M, Winqvist O, Andersson LC (2003) RELP, a novel human REG-like protein with up-regulated expression in inflammatory and metaplastic gastrointestinal mucosa. Am J Pathol 163(1):11–20

    Article  PubMed  PubMed Central  Google Scholar 

  • Kassem SA, Ariel I, Thornton PS, Scheimberg I, Glaser B (2000) β-cell proliferation and apoptosis in the developing normal human pancreas and in hyperinsulinism of infancy. Diabetes 49(8):1325–1333

    Article  CAS  PubMed  Google Scholar 

  • Kato I, Takasawa S, Akabane A, Tanaka O, Abe H, Takamura T, Suzuki Y, Nata K, Yonekura H, Yoshimoto T, Okamoto H (1995) Regulatory role of CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) in insulin secretion by glucose in pancreatic β-cells. Enhanced insulin secretion in CD38-expressing transgenic mice. J Biol Chem 270(50):30045–30050

    Article  CAS  PubMed  Google Scholar 

  • Kato I, Yamamoto Y, Fujimura M, Noguchi N, Takasawa S, Okamoto H (1999) CD38 disruption impairs glucose-induced increases in cyclic ADP-ribose, [Ca2+]i, and insulin secretion. J Biol Chem 274(4):1869–1872

    Article  CAS  PubMed  Google Scholar 

  • Kato Y, Miura Y, Yamamoto N, Ozaki N, Oiso Y (2003) Suppressive effects of a selective inducible nitric oxide synthase (iNOS) inhibitor on pancreatic beta-cell dysfunction. Diabetologia 46(9):1228–1233

    Article  CAS  PubMed  Google Scholar 

  • Kauppinen TM, Suh SW, Berman AE, Hamby AM, Swanson RA (2009) Inhibition of poly(ADP-ribose) polymerase suppresses inflammation and promotes recovery after ischemic injury. J Cereb Blood Flow Matab 29(4):820–829

    Article  CAS  Google Scholar 

  • Kazumori H, Ishirara S, Hoshino E, Kawashima K, Moriyama N, Suetsugu H, Sato H, Adachi K, Fukuda R, Watanabe M, Takasawa S, Okamoto H, Fukui H, Chiba T, Kinoshita Y (2000) Neutrophil chemoattractant 2β regulates expression of the Reg gene in injured gastric mucosa in rats. Gastroenterology 119(6):1610–1622

    Article  CAS  PubMed  Google Scholar 

  • Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26(4):239–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kiji T, Dohi Y, Takasawa S, Okamoto H, Nonomura A, Taniguchi S (2005) Activation of regenerating gene Reg in rat and human hearts in response to acute stress. Am J Physiol Heart Circ Physiol 289(1):H277–H284

    Article  CAS  PubMed  Google Scholar 

  • Kim HA, Pomeroy SL, Whoriskey W, Pawlitzky I, Benowitz LI, Sicinski P, Stiles CD, Roberts TM (2000) A developmentally regulated switch directs regenerative growth of Schwann cells through cyclin D1. Neuron 26(2):405–416

    Article  CAS  PubMed  Google Scholar 

  • Kim HA, Ratner N, Roberts TM, Stiles CD (2001) Schwann cell proliferative responses to cAMP and Nf1 are mediated by cyclin D1. J Neurosci 21(4):1110–1116

    CAS  PubMed  Google Scholar 

  • Kim BJ, Park KH, Yim CY, Takasawa S, Okamoto H, Im MJ, Kim UH (2008) Generation of nicotinic acid adenine dinucleotide phosphate and cyclic ADP-ribose by glucagon-like peptide-1 evokes Ca2+ signal that is essential for insulin secretion in mouse pancreatic islets. Diabetes 57(4):868–878

    Article  CAS  PubMed  Google Scholar 

  • Klasan GS, Ivanac D, Erzen DJ, Picard A, Takasawa S, Peharec S, Arbanas J, Girotto D, Jerkovic R (2014) Reg3G gene expression in regenerating skeletal muscle and corresponding nerve. Muscle Nerve 49(1):61–68

    Article  CAS  PubMed  Google Scholar 

  • Knip M, Douek IF, Moore WP, Gillmor HA, McLean AE, Bingley PJ, Gale EA, European Nicotinamide Diabetes Intervention Trial Group (2000) Safety of high-dose nicotinamide: a review. Diabetologia 43(11):1337–1345

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi S, Akiyama T, Nata K, Abe M, Tajima M, Shervani NJ, Unno M, Matsuno S, Sasaki H, Takasawa S, Okamoto H (2000) Identification of a receptor for Reg (Regenerating gene) protein, a pancreatic β-cell regeneration factor. J Biol Chem 275(15):10723–10726

    Article  CAS  PubMed  Google Scholar 

  • Koguma T, Takasawa S, Tohgo A, Karasawa T, Furuya Y, Yonekura H, Okamoto H (1994) Cloning and characterization of cDNA encoding rat ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase (homologue to human CD38) from islets of Langerhans. Biochim Biophys Acta 1223(1):160–162

    Article  CAS  PubMed  Google Scholar 

  • Kordula T, Travis J (1996) The role of Stat and C/EBP transcription factors in the synergistic activation of rat serine protease inhibitor-3 gene by interleukin-6 and dexamethasone. Biochem J 313(Pt 3):1019–1027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kroemer G, El-Deiry WS, Golstein P, Peter ME, Vaux D, Vandenabeele P, Zhivotovsky B, Blagosklonny MV, Malorni W, Knight RA, Piacentini M, Nagata S, Melino G (2005) Classification of cell death: recommendations of the Nomenclature Committee on Cell Death. Cell Death Differ 12(suppl 2):1463–1467

    Article  CAS  PubMed  Google Scholar 

  • Kröncke KD, Fehsel K, Sommer A, Rodriguez ML, Kolb-Bachofen V (1995) Nitric oxide generation during cellular metabolization of the diabetogenic N-methyl-N-nitroso-urea streptozotozin contributes to islet cell DNA damage. Biol Chem Hoppe Seyler 376(3):179–185

    Article  PubMed  Google Scholar 

  • Lasserre C, Simon MT, Ishikawa H, Diriong S, Nguyen VC, Christa L, Vernier P, Brechot C (1994) Structural organization and chromosomal localization of a human gene (HIP/PAP) encoding a C-type lectin overexpressed in primary liver cancer. Eur J Biochem 224(1):29–38

    Article  CAS  PubMed  Google Scholar 

  • LeDoux SP, Woodley SE, Patton NJ, Wilson GL (1986) Mechanisms of nitrosourea-induced beta-cell damage. Alterations in DNA. Diabetes 35(8):866–872

    Article  CAS  PubMed  Google Scholar 

  • Leonardi O, Mints G, Hussain MA (2003) Beta-cell apoptosis in the pathogenesis of human type 2 diabetes mellitus. Eur J Endocrinol 148(2):99–102

    Article  Google Scholar 

  • Levine JL, Patel KJ, Zheng Q, Shuldiner AR, Zenilman ME (2000) A recombinant rat regenerating protein is mitogenic to pancreatic derived cells. J Surg Res 89(1):60–65

    Article  CAS  PubMed  Google Scholar 

  • Li B, Luo C, Chowdhury S, Gao Z-H, Liu J-L (2013) Parp1 deficient mice are protected from streptozotocin-induced diabetes but not caerulein-induced pancreatitis, independent of the induction of Reg family genes. Regul Pept 186:83–91

    Article  CAS  PubMed  Google Scholar 

  • Liaudet L, Soriano FG, Szabó E, Virág L, Mabley JG, Salzman AL, Szabo C (2000) Protection against hemorrhagic shock in mice genetically deficient in poly(ADP-ribose)polymerase. Proc Natl Acad Sci USA 97(18):10203–10208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Livesey FJ, O’Brien JA, Li M, Smith AG, Murphy LJ, Hunt SP (1997) A Schwann cell mitogen accompanying regeneration of motor neurons. Nature 390(6660):614–618

    Article  CAS  PubMed  Google Scholar 

  • Lu Y, Ponton A, Okamoto H, Takasawa S, Herrera PL, Liu JL (2006) Activation of the Reg family genes by pancreatic-specific IGF-I gene deficiency and after streptozotocin-induced diabetes in mouse pancreas. Am J Physiol Endocrinol Metab 291(1):E50–E58

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Makino S, Kunimoto K, Muraoka Y, Mizushima Y, Katagiri K, Tochino Y (1980) Breeding of a non-obese diabetic strain of mice. Jikken Dobutsu 29(1):1–13

    CAS  PubMed  Google Scholar 

  • Malaisse WJ, Malaisse-Lagae F, Sener A, Pipeleers DG (1982) Determinants of the selective toxicity of alloxan to the pancreatic B cell. Proc Natl Acad Sci USA 79(3):927–930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mallone R, Ortolan E, Baj G, Funaro A, Giunti S, Lillaz E, Saccucci F, Cassader M, Cavallo-Perin P, Malavasi F (2001) Autoantibody response to CD38 in Caucasian patients with type 1 and type 2 diabetes: immunological and genetic characterization. Diabetes 50(4):752–762

    Article  CAS  PubMed  Google Scholar 

  • Marchetti P, Antonelli A, Lupi R, Marselli L, Fallahi P, Nesti C, Baj G, Ferrannini E (2002) Prolonged in vitro exposure to autoantibodies against CD38 impairs the function and survival of human pancreatic islets. Diabetes 51(suppl 3):S474–S477

    Article  CAS  PubMed  Google Scholar 

  • Marchetti P, Del Prato S, Lupi R, Del Guerra S (2006) The pancreatic beta-cell in human Type 2 diabetes. Nutr Metab Cardiovasc Dis 16(Suppl 1):S3–S6

    Article  PubMed  Google Scholar 

  • Martin DR, Lewington AJ, Hammerman MR, Padanilam BJ (2000) Inhibition of poly(ADP-ribose) polymerase attenuates ischemic renal injury in rats. Am J Physiol Integr Comp Physiol 279(5):R1834–R1840

    CAS  Google Scholar 

  • Martin S, van den Engel NK, Vinke A, Heidenthal E, Schulte K, Kolb H (2001) Dominant role of intercellular adhesion molecule-1 in the pathogenesis of autoimmune diabetes in non-obese diabetic mice. J Autoimmun 17(2):109–117

    Article  CAS  PubMed  Google Scholar 

  • Marx J (2002) Nobel Prize in Physiology or Medicine. Tiny worm takes a star turn. Science 298(5593):526

    Article  PubMed  Google Scholar 

  • Masiello P, Novelli M, Fierabracci V, Bergamini E (1990) Protection by 3-aminobenzamide and nicotinamide against streptozotocin-induced beta-cell toxicity in vivo and in vitro. Res Commun Chem Pathol Pharmacol 69(1):17–32

    CAS  PubMed  Google Scholar 

  • Masutani M, Suzuki H, Kamada N, Watanabe M, Ueda O, Nozaki T, Jishage K, Watanabe T, Sugimoto T, Nakagama H, Ochiya T, Sugimura T (1999) Poly(ADP-ribose) polymerase gene disruption conferred mice resistant to streptozotocin-induced diabetes. Proc Natl Acad Sci USA 96(5):2301–2304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuoka T, Kajimoto Y, Watada H, Umayahara Y, Kubota M, Kawamori R, Yamasaki Y, Kamada T (1995) Expression of CD38 gene, but not of mitochondrial glycerol-3-phosphate dehydrogenase gene, is impaired in pancreatic islets of GK rats. Biochem Biophys Res Commun 214(1):239–246

    Article  CAS  PubMed  Google Scholar 

  • Matsuura S, Egi Y, Yuki S, Horikawa T, Satoh H, Akira T (2011) MP-124, a novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor, ameliorates ischemic brain damage in a non-human primate model. Brain Res 1410:122–131

    Article  CAS  PubMed  Google Scholar 

  • McCord JM, Fridovich I (1969) Superoxide dismutase. An enzymic function for erythrocuprein (Hemocuprein). J Biol Chem 244(22):6049–6055

    CAS  PubMed  Google Scholar 

  • Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M (2012) IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (Lond) 122(4):143–159

    Article  CAS  Google Scholar 

  • Mitchell KJ, Pinton P, Varadi A, Tacchetti C, Ainscow EK, Pozzan T, Rizzuto R, Rutter GA (2001) Dense core secretory vesicles revealed as a dynamic Ca2+ store in neuroendocrine cells with a vesicle-associated membrane protein aequorin chimaera. J Cell Biol 155(1):41–51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyashita H, Nakagawara K, Mori M, Narushima Y, Noguchi N, Moriizumi S, Takasawa S, Yonekura H, Takeuchi T, Okamoto H (1995) Human REG family genes are tandemly ordered in a 95-kilobase region of chromosome 2p12. FEBS Lett 377(3):429–433

    Article  CAS  PubMed  Google Scholar 

  • Modak MA, Datar SP, Bhonde RR, Ghaskadbi SS (2007) Differential susceptibility of chick and mouse islets to streptozotocin and its co-relation with islet antioxidant status. J Comp Physiol B 177(2):247–257

    Article  CAS  PubMed  Google Scholar 

  • Montane J, Cadavez L, Novials A (2014) Stress and the inflammatory process: a major cause of pancreatic cell death in type 2 diabetes. Diabtes Metab Syndr Obes 7:25–34

    CAS  Google Scholar 

  • Mori Y, Suko M, Okudaira H, Matsuba I, Tsuruoka A, Sasaki A, Yokoyama H, Tanase T, Shida T, Nishimura M, Terada E, Ikeda Y (1986) Preventive effects of cyclosporine on diabetes in NOD mice. Diabetologia 29(4):244–247

    Article  CAS  PubMed  Google Scholar 

  • Moriizumi S, Watanabe T, Unno M, Nakagawara K, Suzuki Y, Miyashita H, Yonekura H, Okamoto H (1994) Isolation, structural determination and expression of a novel reg gene, human reg Iβ. Biochim Biophys Acta 1217(2):199–202

    Article  CAS  PubMed  Google Scholar 

  • Moriscot C, Renaud W, Bouvier R, Figarella-Branger D, Figarella C, Guy-Crotte O (1996) Absence of correlation between reg and insulin gene expression in pancreas during fetal development. Pediatr Res 39(2):349–353

    Article  CAS  PubMed  Google Scholar 

  • Nagatani S, Sudo T, Murakami Y, Uemura K, Hiyama E, Sueda T (2011) Edaravone, a free radical scavenger, promotes engraftment of intraportally transplanted islet cells. Pancreas 40(1):126–130

    Article  CAS  PubMed  Google Scholar 

  • Nakagawa K, Takasawa S, Nata K, Yamauchi A, Itaya-Hironaka A, Ota H, Yoshimoto K, Sakuramoto-Tsuchida S, Miyaoka T, Takeda M, Unno M, Okamoto H (2013) Prevention of Reg I-induced β-cell apoptosis by IL-6/dexamethasone through activation of HGF gene regulation. Biochim Biophys Acta 1833(12):2988–2995

    Article  CAS  PubMed  Google Scholar 

  • Namikawa K, Fukushima M, Murakami K, Suzuki A, Takasawa S, Okamoto H, Kiyama H (2005) Expression of Reg/PAP family members during motor nerve regeneration in rat. Biochem Biophys Res Commun 332(1):126–134

    Article  CAS  PubMed  Google Scholar 

  • Narushima Y, Unno M, Nakagawara K, Mori M, Miyashita H, Suzuki Y, Noguchi N, Takasawa S, Kumagai T, Yonekura H, Okamoto H (1997) Structure, chromosomal localization and expression of mouse genes encoding type III Reg, Reg IIIα, Reg IIIβ. Reg IIIγ. Gene 185(2):159–168

    Article  CAS  PubMed  Google Scholar 

  • Nata K, Takamura T, Karasawa T, Kumagai T, Hashioka W, Tohgo A, Yonekura H, Takasawa S, Nakamura S, Okamoto H (1997) Human gene encoding CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase): organization, nucleotide sequence and alternative splicing. Gene 186(2):285–292

    Article  CAS  PubMed  Google Scholar 

  • Nata K, Liu Y, Xu L, Ikeda T, Akiyama T, Noguchi N, Kawaguchi S, Yamauchi A, Takahashi I, Shervani NJ, Onogawa T, Takasawa S, Okamoto H (2004) Molecular cloning, expression and chromosomal localization of a novel human REG family gene. REG III. Gene 340(1):161–170

    Article  CAS  PubMed  Google Scholar 

  • Nishimune H, Vasseur S, Wiese S, Birling MC, Holtmann B, Sendtner M, Iovanna JL, Henderson CE (2000) Reg-2 is a motoneuron neurotrophic factor and a signalling intermediate in the CNTF survival pathway. Nature Cell Biol 2(12):906–914

    Article  CAS  PubMed  Google Scholar 

  • Nishizuka Y, Ueda K, Nakazawa K, Hayaishi O (1967) Studies on the polymer of adenosine diphosphate ribose. I. Enzymic formation from nicotinamide adenine dinucleotide in mammalian nuclei. J Biol Chem 242(13):3164–3171

    CAS  PubMed  Google Scholar 

  • Noguchi N, Takasawa S, Nata K, Tohgo A, Kato I, Ikehata F, Yonekura H, Okamoto H (1997) Cyclic ADP-ribose binds to FK506-binding protein 12.6 to release Ca2+ from islet microsomes. J Biol Chem 272(6):3133–3136

    Article  CAS  PubMed  Google Scholar 

  • Noguchi N, Yoshikawa T, Ikeda T, Takahashi I, Shervani NJ, Uruno A, Yamauchi A, Nata K, Takasawa S, Okamoto H, Sugawara A (2008) FKBP12.6 disruption impairs glucose-induced insulin secretion. Biochem Biophys Res Commun 371(4):735–740

    Article  CAS  PubMed  Google Scholar 

  • Nomikos IN, Prowse SJ, Carotenuto P, Lafferty KJ (1986) Combined treatment with nicotinamide and desferrioxamine prevents islet allograft destruction in NOD mice. Diabetes 35(11):1302–1304

    Article  CAS  PubMed  Google Scholar 

  • Notkins AL, Lernmark A (2001) Autoimmune type 1 diabetes: resolved and unresolved issues. J Clin Invest 108(9):1247–1252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohta Y, Kitanaka A, Mihara K, Imataki O, Ohnishi H, Tanaka T, Taminato T, Kubota Y (2011) Expression of CD38 with intracellular enzymatic activity: a possible explanation for the insulin release induced by intracellular cADPR. Mol Cell Biochem 352(1–2):293–299

    Article  CAS  PubMed  Google Scholar 

  • Okamoto H (1981) Regulation of proinsulin synthesis in pancreatic islets and a new aspect to insulin-dependent diabetes. Mol Cell Biochem 37(1):43–61

    Article  CAS  PubMed  Google Scholar 

  • Okamoto H (1985) Molecular basis of experimental diabetes: degeneration, oncogenesis and regeneration of pancreatic B-cells of islets of Langerhans. BioEssays 2:15–21

    Article  CAS  Google Scholar 

  • Okamoto H Sr (1976) Antitumor activity of streptolysin S-forming streptococci. In: Bernheimer AW (ed) Mechanisms in bacterial toxicology. Wiley, New York, pp 237–257

    Google Scholar 

  • Okamoto H, Takasawa S (2002) Recent advances in the Okamoto model: the CD38-cyclic ADP-ribose signal system and the regenerating gene protein (Reg)-Reg receptor system in β-cells. Diabetes 51(suppl 3):S462–S473

    Article  CAS  PubMed  Google Scholar 

  • Okamoto H, Takasawa S (2003) Recent advances in physiological and pathological significance of NAD+ metabolites: roles of poly(ADP-ribose) and cyclic ADP-ribose in insulin secretion and diabetogenesis. Nutr Res Rev 16(2):253–266

    Article  CAS  PubMed  Google Scholar 

  • Okamoto H, Takasawa S, Nata K (1997) The CD38-cyclic ADP-ribose signaling system in insulin secretion: molecular basis and clinical implications. Diabetologia 40(12):1485–1491

    Article  CAS  PubMed  Google Scholar 

  • Oliver FJ, Ménissier-de Murcia J, Nacci C, Decker P, Andriantsitohaina R, Muller S, de la Rubia G, Stoclet JC, de Murcia G (1999) Resistance to endotoxic shock as a consequence of defective NF-κB activation in poly (ADP-ribose) polymerase-1 deficient mice. EMBO J 18(16):4446–4454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Omori K, Matsuda T, Ferreri K, Todorov I, Okamoto H, Takasawa S, Kandeel F, Mullen Y (2003) Induction of REG gene expression, in vitro, in human islets. Transplantation 76(4):S59

    Article  Google Scholar 

  • Ota H, Tamaki S, Itaya-Hironaka A, Yamauchi A, Sakuramoto-Tsuchida S, Morioka T, Takasawa S, Kimura H (2012) Attenuation of glucose-induced insulin secretion by intermittent hypoxia via down-regulation of CD38. Life Sci 90(5–6):206–211

    Article  CAS  PubMed  Google Scholar 

  • Ota H, Itaya-Hironaka A, Yamauchi A, Sakuramoto-Tsuchida S, Miyaoka T, Fujimura T, Tsujinaka H, Yoshimoto K, Nakagawara K, Tamaki S, Takasawa S, Kimura H (2013) Pancreatic β-cell proliferation by intermittent hypoxia via up-regulation of Reg family genes and HGF gene. Life Sci 93(18–19):664–672

    Article  CAS  PubMed  Google Scholar 

  • Pacher P, Szabó C (2007) Role of poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: the therapeutic potential of PARP inhibitors. Cardiovasc Drug Rev 25(3):235–260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pacher P, Liaudet L, Soriano FG, Mabley JG, Szabó É, Szabó C (2002) The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes. Diabetes 51(2):514–521

    Article  CAS  PubMed  Google Scholar 

  • Pandya KG, Patel MR, Lau-Cam CA (2010) Comparative study of the binding characteristics to and inhibitory potencies towards PARP and in vivo antidiabetogenic potencies of taurine, 3-aminobenzamide and nicotinamide. J Biomed Sci 17(suppl 1):S16

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pieper AA, Brat DJ, Krug DK, Watkins CC, Gupta A, Blackshaw S, Verma A, Wang Z-Q, Snyder SH (1999) Poly(ADP-ribose) polymerase-deficient mice are protected from streptozotocin-induced diabetes. Proc Natl Acad Sci USA 96(6):3059–3064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pieper AA, Walles T, Wei G, Clements EE, Verma A, Snyder SH, Zweier JL (2000) Myocardial postischemic injury is reduced by polyADPripose polymerase-1 gene disruption. Mol Med 6(4):271–282

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pimenta W, Korytkowski M, Mitrakou A, Jenssen T, Yki-Jarvinen H, Evron W, Dailey G, Gerich J (1995) Pancreatic beta-cell dysfunction as the primary genetic lesion in NIDDM. JAMA 273(23):1855–1861

    Article  CAS  PubMed  Google Scholar 

  • Pirsch JD, Miller J, Deierhoi MH, Vincenti F, Filo RS (1997) A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group. Transplantation 63(7):977–983

    Article  CAS  PubMed  Google Scholar 

  • Planas R, Alba A, Carrillo J, Puertas MC, Ampudia R, Pastor X, Okamoto H, Takasawa S, Gurr W, Pujol-Borrell R, Verdaguer J, Vives-Pi M (2006) Reg (regenerating) gene overexpression in islets from non-obese diabetic mice with accelerated diabetes: role of IFNβ. Diabetologia 49(10):2379–2387

    Article  CAS  PubMed  Google Scholar 

  • Plaschke K, Kopitz J, Weigand MA, Martin E, Bardenheuer HJ (2000) The neuroprotective effect of cerebral poly(ADP-ribose)polymerase inhibition in a rat model of global ischemia. Neurosci Lett 284(1–2):109–112

    Article  CAS  PubMed  Google Scholar 

  • Pupilli C, Giannini S, Marchetti P, Lupi R, Antonelli A, Malavasi F, Takasawa S, Okamoto H, Ferrannini E (1999) Autoantibodies to CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) in Caucasian patients with diabetes: effects on insulin release from human islets. Diabetes 48(12):2309–2315

    Article  CAS  PubMed  Google Scholar 

  • Rakieten N, Rakieten ML, Nadkarni MR (1963) Studies on the diabetogenic action of streptozotocin (NSC-37917). Cancer Chemother Rep 29:91–98

    Google Scholar 

  • Rane SG, Dubus P, Mettus RV, Galbreath EJ, Boden G, Reddy EP, Barbacid M (1999) Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in beta-islet cell hyperplasia. Nature Genet 22(1):44–52

    Article  CAS  PubMed  Google Scholar 

  • Reddy S, Karanam M, Robinson E (2001) Prevention of cyclophosphamide-induced accelerated diabetes in the NOD mouse by nicotinamide or a soy protein-based infant formula. Int J Exp Diabetes Res 1(4):299–313

    Article  CAS  PubMed  Google Scholar 

  • Rhodes CJ (2005) Type 2 diabetes—a matter of β-cell life and death? Science 307(5708):380–384

    Article  CAS  PubMed  Google Scholar 

  • Roesner JP, Mersmann J, Bergt S, Bohnenberg K, Barthuber C, Szabo C, Nöldge-Schomburg GE, Zacharowski K (2010) Therapeutic injection of PARP inhibitor INO-1001 preserves cardiac function in porcine myocardial ischemia and reperfusion without reducing infarct size. Shock 33(5):507–512

    Article  CAS  PubMed  Google Scholar 

  • Rossi D, Sorrentino V (2010) The multiple alternatives of intracellular calcium signaling: a functionally distinct RyR splicing variant in pancreatic islets. Islets 2(6):383–385

    Article  PubMed  Google Scholar 

  • Roza AM, Slakey DP, Pieper GM, Van Ye TM, Moore-Hilton G, Komorowski RA, Johnson CP, Hedlund BE, Adams MB (1994) Hydroxyethyl starch deferoxamine, a novel iron chelator, delays diabetes in BB rats. J Lab Clin Med 123(4):556–560

    CAS  PubMed  Google Scholar 

  • Rutter GA, Theler JM, Li G, Wolheim CB (1994) Ca2+ stores in insulin-secreting cells: lack of effect of cADP ribose. Cell Calcium 16(2):71–80

    Article  CAS  PubMed  Google Scholar 

  • Sakuraba H, Mizukami H, Yagihashi N, Wada R, Hanyu C, Yagihashi S (2002) Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients. Diabetologia 45(1):85–96

    Article  CAS  PubMed  Google Scholar 

  • Sasamori K, Sasaki T, Takasawa S, Tamada T, Nara M, Irokawa T, Shimura S, Shirato K, Hattori T (2004) Cyclic ADP-ribose, a putative Ca2+-mobilizing second messenger, operates in submucosal gland acinar cells. Am J Physiol Lung Cell Mol Physiol 287(1):L69–L78

    Article  CAS  PubMed  Google Scholar 

  • Satoh J, Shintani S, Oya K, Tanaka S, Nobunaga T, Toyota T, Goto Y (1988) Treatment with streptococcal preparation (OK-432) suppresses anti-islet autoimmunity and prevents diabetes in BB rats. Diabetes 37(9):1188–1194

    Article  CAS  PubMed  Google Scholar 

  • Satomura Y, Sawabu N, Mouri I, Yamakawa O, Watanabe H, Motoo Y, Okai T, Ito T, Kaneda K, Okamoto H (1995) Measurement of serum PSP/reg-protein concentration in various diseases with a newly developed enzyme-linked immunosorbent assay. J Gastroenterol 30(5):643–650

    Article  CAS  PubMed  Google Scholar 

  • Sauter B, Albert ML, Francisco L, Larsson M, Somersan S, Bhardwaj N (2000) Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med 191(3):423–434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schein PS, Cooney DA, Vernon ML (1967) The use of nicotinamide to modify the toxicity of streptozotocin diabetes without loss of antitumor activity. Cancer Res 27(12):2324–2332

    CAS  PubMed  Google Scholar 

  • Seino H, Satoh J, Shintani S, Takahashi K, Zhu XP, Masuda T, Nobunaga T, Saito M, Terano Y, Toyota T (1991) Inhibition of autoimmune diabetes in NOD mice with serum from streptococcal preparation (OK-432)-injected mice. Clin Exp Immunol 86(3):413–418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sekine N, Ishikawa T, Okazaki T, Hayashi M, Wollheim CB, Fujita T (2000) Synergistic activation of NF-κΒ and inducible isoform of nitric oxide synthase induction by interferon-γ and tumor necrosis factor-α in INS-1 cells. J Cell Physiol 184(1):46–57

    Article  CAS  PubMed  Google Scholar 

  • Shervani NJ, Takasawa S, Uchigata Y, Akiyama T, Nakagawa K, Noguchi N, Takada H, Takahashi I, Yamauchi A, Ikeda T, Iwamoto Y, Nata K, Okamoto H (2004) Autoantibodies to REG, a beta-cell regeneration factor, in diabetic patients. Eur J Clin Invest 34(11):752–758

    Article  CAS  PubMed  Google Scholar 

  • Skarda DE, Putt KS, Hergenrother PJ, Mulier KE, Beilman GJ (2007) Increased poly(ADP-ribose) polymerase activity during porcine hemorrhagic shock is transient and predictive of mortality. Resuscitation 75(1):135–144

    Article  CAS  PubMed  Google Scholar 

  • Smith FE, Bonner-Weir S, Leahy JL, Laufgraben MJ, Ogawa Y, Rosen KM, Villa-Komaroff L (1994) Pancreatic Reg/pancreatic stone protein (PSP) gene expression does not correlate with beta-cell growth and regeneration in rats. Diabetologia 37(10):994–999

    Article  CAS  PubMed  Google Scholar 

  • Soriano GF, Virág L, Jagtap P, Szabó É, Mabley JG, Liaudet J, Marton A, Hoyt DG, Murthy KGK, Salzman AL, Southan GJ, Szabó C (2001) Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation. Nat Med 7(1):108–113

    Article  CAS  Google Scholar 

  • Stern Y, Salzman A, Cotton RT, Zingarelli B (1999) Protective effect of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase, against laryngeal injury in rats. Am J Respir Crit Care Med 160(5 Pt 1):1743–1749

    Article  CAS  PubMed  Google Scholar 

  • Suarez-Pinzon WL, Mabley JG, Strynadka K, Power RF, Szabó C, Rabinovitch A (2001) An inhibitor of inducible nitric oxide synthase and scavenger of peroxynitrite prevents diabetes development in NOD mice. J Autoimmun 16(4):449–455

    Article  CAS  PubMed  Google Scholar 

  • Sugimura T, Fujimura S, Hasegawa S, Kawamura Y (1967) Polymerization of the adenosine 5’-diphosphate ribose moiety of NAD by rat liver nuclear enzyme. Biochim Biophys Acta 138(2):438–441

    Article  CAS  PubMed  Google Scholar 

  • Suzuki H, Takasawa S, Usui I, Ishii Y, Kato I, Okamoto H, Kobayashi M, Sasahara M, Tobe K (2014) The Ca2+/calmodulin-dependent protein kinase IIα (Thr286Asp) transgenic mice: a novel mouse model of severe insulin-dependent diabetes. Austin J Endocrinol Diabet 1(1):9

    Google Scholar 

  • Szabó C, Cuzzocrea S, Zingarelli B, O’Connor M, Salzman AL (1997) Endothelial dysfunction in a rat model of endotoxic shock. Importance of the activation of poly (ADP-ribose) synthetase by peroxynitrite. J Clin Invest 100(3):723–735

    Article  PubMed  PubMed Central  Google Scholar 

  • Szabó G, Liaudet L, Hagl S, Szabó C (2004) Poly(ADP-ribose) polymerase activation in the reperfused myocardium. Cardiovasc Res 61(3):471–480

    Article  PubMed  CAS  Google Scholar 

  • Takahashi K, Satoh J, Seino H, Zhu XP, Sagara M, Masuda T, Toyota T (1993) Prevention of type I diabetes with lymphotoxin in BB rats. Clin Immunol Immunopathol 69(3):318–323

    Article  CAS  PubMed  Google Scholar 

  • Takamura T, Kato I, Kimura N, Nakazawa T, Yonekura H, Takasawa S, Okamoto H (1998) Transgenic mice overexpressing type 2 nitric-oxide synthase in pancreatic β-cells develop insulin-dependent diabetes without insulitis. J Biol Chem 273(5):2493–2496

    Article  CAS  PubMed  Google Scholar 

  • Takasawa S, Okamoto H (2002) Pancreatic β-cell death, regeneration and insulin Secretion: roles of poly(ADP-ribose) polymerase and cyclic ADP-ribose. Int J Exp Diabetes Res 3(2):79–96

    Article  PubMed  PubMed Central  Google Scholar 

  • Takasawa S, Yamamoto H, Terazono K, Okamoto H (1986) Novel gene activated in rat insulinomas. Diabetes 35(10):1178–1180

    Article  CAS  PubMed  Google Scholar 

  • Takasawa S, Nata K, Yonekura H, Okamoto H (1993a) Cyclic ADP-ribose in insulin secretion from pancreatic β-cells. Science 259(5093):370–373

    Article  CAS  PubMed  Google Scholar 

  • Takasawa S, Nata K, Yonekura H, Okamoto H (1993b) Cyclic ADP-ribose in β-cells: Response. Science 262(5133):585

    Article  CAS  PubMed  Google Scholar 

  • Takasawa S, Tohgo A, Noguchi N, Koguma T, Nata K, Sugimoto T, Yonekura H, Okamoto H (1993c) Synthesis and hydrolysis of cyclic ADP-ribose by human leukocyte antigen CD38 and inhibition of the hydrolysis by ATP. J Biol Chem 268(35):26052–26054

    CAS  PubMed  Google Scholar 

  • Takasawa S, Ishida A, Nata K, Nakagawa K, Noguchi N, Tohgo A, Kato I, Yonekura H, Fujisawa H, Okamoto H (1995) Requirement of calmodulin-dependent protein kinase II in cyclic ADP-ribose-mediated intracellular Ca2+ mobilization. J Biol Chem 270(51):30257–30259

    Article  CAS  PubMed  Google Scholar 

  • Takasawa S, Akiyama T, Nata K, Kuroki M, Tohgo A, Noguchi N, Kobayashi S, Kato I, Katada T, Okamoto H (1998) Cyclic ADP-ribose and inositol 1,4,5-trisphosphate as alternate second messengers for intracellular Ca2+ mobilization in normal and diabetic β-cells. J Biol Chem 273(5):2497–2500

    Article  CAS  PubMed  Google Scholar 

  • Takasawa S, Ikeda T, Akiyama T, Nata K, Nakagawa K, Shervani NJ, Noguchi N, Murakami-Kawaguchi S, Yamauchi A, Takahashi I, Tomioka-Kumagai T, Okamoto H (2006) Cyclin D1 activation through ATF-2 in Reg-induced pancreatic β-cell regeneration. FEBS Lett 580(2):585–591

    Article  CAS  PubMed  Google Scholar 

  • Takasawa S, Kuroki M, Nata K, Noguchi N, Ikeda T, Yamauchi A, Ota H, Itaya-Hironaka A, Sakuramoto-Tsuchida S, Takahashi I, Yoshikawa T, Shimosegawa T, Okamoto H (2010) A novel ryanodine receptor expressed in pancreatic islets by alternative splicing from type 2 ryanodine receptor gene. Biochem Biophys Res Commun 397(2):140–145

    Article  CAS  PubMed  Google Scholar 

  • Takasu N, Asawa T, Komiya I, Nagasawa Y, Yamada T (1991) Alloxan-induced DNA strand breaks in pancreatic islets. Evidence for H2O2 as an intermediate. J Biol Chem 266(4):2112–2114

    CAS  PubMed  Google Scholar 

  • Terazono K, Yamamoto H, Takasawa S, Shiga K, Yonemura Y, Tochino Y, Okamoto H (1988) A novel gene activated in regenerating islets. J Biol Chem 263(5):2111–2114

    CAS  PubMed  Google Scholar 

  • Thomas HE, Darwiche R, Corbett JA, Kay TW (2002) Interleukin-1 plus γ-interferon-induced pancreatic β-cell dysfunction is mediated by β-cell nitric oxide production. Diabetes 51(2):311–316

    Article  CAS  PubMed  Google Scholar 

  • Thompson CB (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267(5203):1456–1462

    Article  CAS  PubMed  Google Scholar 

  • Tjälve H, Wilander E, Johansson E (1976) Distribution of labelled streptozotocin in mice: uptake and retention in pancreatic islets. J Endocrinol 69(3):455–456

    Article  PubMed  Google Scholar 

  • Todd JA (2010) Etiology of type 1 diabetes. Immunity 32(4):457–467

    Article  CAS  PubMed  Google Scholar 

  • Todd JA, Knip M, Mathieu C (2011) Strategies for the prevention of autoimmune type 1 diabetes. Diabet Med 28(10):1141–1143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tohgo A, Takasawa S, Noguchi N, Koguma T, Nata K, Sugimoto T, Furuya Y, Yonekura H, Okamoto H (1994) Essential cysteine residues for cyclic ADP-ribose synthesis and hydrolysis by CD38. J Biol Chem 269(46):28555–28557

    CAS  PubMed  Google Scholar 

  • Tohgo A, Munakata H, Takasawa S, Nata K, Akiyama T, Hayashi N, Okamoto H (1997) Lysine 129 of CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) participates in the binding of ATP to inhibit the cyclic ADP-ribose hydrolase. J Biol Chem 272(7):3879–3882

    Article  CAS  PubMed  Google Scholar 

  • Toniolo A, Onodera T, Yoon J-W, Notkins AL (1980) Induction of diabetes by cumulative environmental insulitis from viruses and chemicals. Nature 288(5789):383–385

    Article  CAS  PubMed  Google Scholar 

  • Toyota T, Satoh J, Oya K, Shintani S, Okano T (1986) Streptococcal preparation (OK-432) inhibits development of type I diabetes in NOD mice. Diabetes 35(4):496–499

    Article  CAS  PubMed  Google Scholar 

  • Tsubouchi S, Suzuki H, Ariyoshi H, Matsuzawa T (1981) Radiation-induced acute necrosis of the pancreatic islet and the diabetic syndrome in the golden hamster (Mesocricetus auratus). Int J Radiat Biol Relat Stud Phys Chem Med 40(1):95–106

    CAS  PubMed  Google Scholar 

  • Uchigata Y, Yamamoto H, Kawamura A, Okamoto H (1982) Protection by superoxide dismutase, catalase, and poly(ADP-ribose) synthetase inhibitors against alloxan- and streptozotocin-induced islet DNA strand breaks and against the inhibition of proinsulin synthesis. J Biol Chem 257(11):6084–6088

    CAS  PubMed  Google Scholar 

  • Uchigata Y, Yamamoto H, Nagai H, Okamoto H (1983) Effect of poly(ADP-ribose) synthetase inhibitor administration to rats before and after injection of alloxan and streptozotocin on islet proinsulin synthesis. Diabetes 32(4):316–318

    Article  CAS  PubMed  Google Scholar 

  • Ueda K, Hayaishi O (1985) ADP-ribosylation. Annu Rev Biochem 54:73–100

    Article  CAS  PubMed  Google Scholar 

  • Unno M, Nata K, Noguchi N, Narushima Y, Akiyama T, Ikeda T, Nakagawa K, Takasawa S, Okamoto H (2002) Production and characterization of Reg knockout mice: reduced proliferation of pancreatic β-cells in Reg knockout mice. Diabetes 51(suppl 3):S478–S483

    Article  CAS  PubMed  Google Scholar 

  • Varadi A, Rutter GA (2002) Dynamic imaging of endoplasmic reticulum Ca2+ concentration in insulin-secreting MIN6 Cells using recombinant targeted cameleons: roles of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)-2 and ryanodine receptors. Diabetes 51(Suppl 1):S190–S201

    Article  CAS  PubMed  Google Scholar 

  • Viterbo D, Callender GE, DiMaio T, Mueller CM, Smith-Norowitz T, Zenilman ME, Bluth MH (2009) Administration of anti-Reg I and anti-PAPII antibodies worsens pancreatitis. JOP 10(1):15–23

    PubMed  PubMed Central  Google Scholar 

  • Von Mering J, Minkowski O (1889) Diabetes mellitus nach Pankreasexstirpation. Zbl Klin Med 10:393–394

    Google Scholar 

  • Wada R, Yagihashi S (2004) Nitric oxide generation and poly(ADP ribose) polymerase activation precede beta-cell death in rats with a single high-dose injection of streptozotocin. Virchows Arch 444(4):375–382

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Kim NS, Haince J-F, Kang HC, David KK, Andrabi SA, Poirier GG, Dawson VL, Dawson TM (2011) Poly(ADP-ribose) (PAR) binding to apoptosis-inducing factor is critical for PAR polymerase-1-dependent cell death (parthanatos). Sci Signal 4(167): ra20

    Google Scholar 

  • Watanabe T, Yonekura H, Terazono K, Yamamoto H, Okamoto H (1990) Complete nucleotide sequence of human reg gene and its expression in normal and tumoral tissues. The reg protein, pancreatic stone protein, and pancreatic thread protein are one and the same product of the gene. J Biol Chem 265(13):74732–77439

    Google Scholar 

  • Watanabe T, Yonemura Y, Yonekura H, Suzuki Y, Miyashita H, Sugiyama K, Moriizumi S, Unno M, Tanaka O, Kondo H, Bone AJ, Takasawa S, Okamoto H (1994) Pancreatic beta-cell replication and amelioration of surgical diabetes by Reg protein. Proc Natl Acad Sci USA 91(9):3589–3592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Webb DL, Islam MS, Efanov AM, Brown G, Köhler M, Larsson O, Berggren PO (1996) Insulin exocytosis and glucose-mediated increase in cytoplasmic free Ca2+ concentration in the pancreatic β-cell are independent of cyclic ADP-ribose. J Biol Chem 271(32):19074–19079

    Article  CAS  PubMed  Google Scholar 

  • Wöhler F, Liebig J (1838) Untersuchungen über die Natur der Harnsäure. Ann Pharm 26(3):241–336

    Article  Google Scholar 

  • Yagui K, Shimada F, Mimura M, Hashimoto N, Suzuki Y, Tokuyama Y, Nata K, Tohgo A, Ikehata F, Takasawa S, Okamoto H, Makino H, Saito Y, Kanatsuka A (1998) A missense mutation in the CD38 gene, a novel factor for insulin secretion: association with Type II diabetes mellitus in Japanese subjects and evidence of abnormal function when expressed in vitro. Diabetologia 41(9):1024–1028

    Article  CAS  PubMed  Google Scholar 

  • Yamada K, Nonaka K, Hanafusa T, Miyazaki A, Toyoshima H, Tarui S (1982) Preventive and therapeutic effects of large-dose nicotinamide injections on diabetes associated with insulitis. An observation in nonobese diabetic (NOD) mice. Diabetes 31(9):749–753

    Article  CAS  PubMed  Google Scholar 

  • Yamagami T, Miwa A, Takasawa S, Yamamoto H, Okamoto H (1985) Induction of rat pancreatic B-cell tumors by the combined administration of streptozotocin or alloxan and poly(adenosine diphosphate ribose) synthetase inhibitors. Cancer Res 45(4):1845–1849

    CAS  PubMed  Google Scholar 

  • Yamamoto H, Uchigata Y, Okamoto H (1981a) Streptozotocin and alloxan induce DNA strand breaks and poly(ADP-ribose) synthetase in pancreatic islets. Nature 294(5838):284–286

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto H, Uchigata Y, Okamoto H (1981b) DNA strand breaks in pancreatic islets by in vivo administration of alloxan or streptozotocin. Biochem Biophys Res Commun 103(3):1014–1020

    Article  CAS  PubMed  Google Scholar 

  • Ylipaasto P, Smura T, Gopalacharyulu P, Paananen A, Seppänen-Laakso T, Kaijalainen S, Ahlfors H, Korsgren O, Lakey JR, Lahesmaa R, Piemonti L, Oresic M, Galama J, Roivainen M (2012) Enterovirus-induced gene expression profile is critical for human pancreatic islet destruction. Diabetologia 55(12):3273–3283

    Article  CAS  PubMed  Google Scholar 

  • Yonemura Y, Takashima T, Miwa K, Miyazaki I, Yamamoto H, Okamoto H (1984) Amelioration of diabetes mellitus in partially depancreatized rats by poly(ADP-ribose) synthetase inhibitors. Evidence of islet B-cell regeneration. Diabetes 33(4):401–404

    Article  CAS  PubMed  Google Scholar 

  • Yoon KH, Ko SH, Cho JH, Lee JM, Ahn YB, Song KH, Yoo SJ, Kang MI, Cha BY, Lee KW, Son HY, Kang SK, Kim HS, Lee IK, Bonner-Weir S (2003) Selective β-cell loss and α-cell expansion in patients with Type 2 diabetes mellitus in Korea. J Clin Endocrinol Metab 88(5):2300–2308

    Article  CAS  PubMed  Google Scholar 

  • Zingarelli B, Salzman AL, Szabó C (1998) Genetic disruption of poly (ADP-ribose) synthetase inhibits the expression of P-selectin and intercellular adhesion molecule-1 in myocardial ischemia/reperfusion injury. Circ Res 83(1):85–94

    Article  CAS  PubMed  Google Scholar 

  • Zingarelli B, Szabó C, Salzman AL (1999) Blockade of Poly(ADP-ribose) synthetase inhibits neutrophil recruitment, oxidant generation, and mucosal injury in murine colitis. Gastroenterology 116(2):335–345

    Article  CAS  PubMed  Google Scholar 

  • Zóka A, Műzes G, Somogyi A, Varga T, Szémán B, Al-Aissa Z, Hadarits O, Firneisz G (2013) Altered immune regulation in type 1 diabetes. Clin Dev Immunol 2013:254874

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, Nara Medical University (NMU), Shijo-cho, Kashihara, 634-8521, Japan

    Shin Takasawa, Asako Itaya-Hironaka, Akiyo Yamauchi, Hiroyo Ota, Maiko Takeda, Sumiyo Sakuramoto-Tsuchida, Takanori Fujimura & Hiroki Tsujinaka

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  1. Shin Takasawa
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Correspondence to Shin Takasawa .

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  1. NHMRC Clinical Trials Centre Diabetes and Islet-biology Group, The University of Sydney Faculty of Medicine, Sydney, New South Wales, Australia

    Anandwardhan A. Hardikar

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Takasawa, S. et al. (2016). Regulators of Beta-Cell Death and Regeneration. In: A. Hardikar, A. (eds) Pancreatic Islet Biology. Stem Cell Biology and Regenerative Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-45307-1_6

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