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PMID: 8858209 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Review

The harmony of the spheres: inducible nitric oxide synthase and related genes in pancreatic beta cells.

Diabetologia ·Vol. 39 ·No. 8 ·1996-08-00 ·Pages 875-90

Eizirik DL, Flodström M, Karlsen AE, Welsh N

Abstract

The radical nitric oxide (NO) is a possible mediator of pancreatic beta-cell damage in insulin-dependent diabetes mellitus (IDDM). NO is produced by the enzyme nitric oxide synthase (NOS), in a reaction where arginine is the main substrate. There are different isoforms of NOS, but in the context of immune mediated beta-cell damage the inducible form of NOS (iNOS) is the most relevant. The beta-cell iNOS is similar and encoded by the same gene on chromosome 17 as the iNOS expressed in macrophages and other nucleated cells. iNOS activation depends on gene transcription and de novo enzyme synthesis, and NO seems to induce a negative feedback on iNOS expression. While iNOS mRNA is induced by interleukin-1 beta (IL-1 beta) alone in rodent insulin-producing cells, a combination of two (IL-1 beta + interferon gamma) (IFN-gamma) or three (IL-1 beta + IFN gamma + tumour necrosis factor alpha) cytokines is required for iNOS activation in human pancreatic islets. The promoter region of the murine iNOS gene has at least 25 binding sites for different transcription factors, and the nuclear transcription factor kappa B is necessary for cytokine-induced iNOS transcription in both rodent and human pancreatic islets. The nature of other transcription factors relevant for iNOS regulation in these cells remains to be determined. Induction of iNOS is paralleled by induction of several other cytokine-dependent genes in beta cells, including argininosuccinate synthetase, cyclooxygenase and manganese superoxide dismutase. Some of these genes may contribute to beta-cell damage, while others are probably involved in beta-cell defence and/or repair. Regulation of iNOS and other related genes in beta cells is complex, and differs in several aspects from that observed in macrophages. There are also important differences in iNOS regulation between rodent and human pancreatic islets. A detailed knowledge of the molecular regulation of these genes in beta cells may be instrumental in the development of new approaches to prevent beta-cell destruction in early IDDM.

MeSH Terms
Animals Cytokines/physiology Diabetes Mellitus, Type 1/genetics Enzyme Induction/genetics Gene Expression Regulation, Enzymologic/genetics Humans Islets of Langerhans/enzymology Mice NF-kappa B/metabolism Nitric Oxide Synthase/biosynthesis,genetics Promoter Regions, Genetic RNA, Messenger/biosynthesis,genetics Rats Signal Transduction
Chemicals
Cytokines NF-kappa B RNA, Messenger Nitric Oxide Synthase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Eizirik D L
Department of Metabolism and Endocrinology, Vrije Universiteit Brussel, Belgium.
Flodström M
Karlsen A E
Welsh N
References (162)
162 references, click to expand
  1. Does nitric oxide mediate autoimmune destruction of beta-cells? Possible therapeutic interventions in IDDM.
    Diabetes. 1992 Aug;41(8):897-903 PMID: 1378415
  2. Molecular cloning, structure, and chromosomal localization of the human inducible nitric oxide synthase gene.
    J Biol Chem. 1994 Mar 4;269(9):6765-72 PMID: 7509810
  3. Transcription and translation of inducible nitric oxide synthase in the pancreas of prediabetic BB rats.
    FEBS Lett. 1993 Aug 9;328(1-2):9-12 PMID: 7688327
  4. Polygenic control of autoimmune diabetes in nonobese diabetic mice.
    Nat Genet. 1993 Aug;4(4):404-9 PMID: 8401590
  5. Liposomal delivery of antioxidant enzymes protects against hydrogen peroxide- but not interleukin-1 beta-induced inhibition of glucose metabolism in rat pancreatic islets.
    J Endocrinol. 1994 Oct;143(1):151-6 PMID: 7964313
  6. Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis.
    Nature. 1996 Mar 7;380(6569):75-9 PMID: 8598911
  7. Cytokine signaling through nonreceptor protein tyrosine kinases.
    Science. 1995 Apr 14;268(5208):251-5 PMID: 7716517
  8. Interleukin-1 beta depletes insulin messenger ribonucleic acid and increases the heat shock protein hsp70 in mouse pancreatic islets without impairing the glucose metabolism.
    Endocrinology. 1990 Nov;127(5):2290-7 PMID: 2171911
  9. The inducible form of nitric oxide synthase (iNOS) in insulin-producing cells.
    Diabete Metab. 1994 Mar-Apr;20(2):116-22 PMID: 7528693
  10. Nicotinamide inhibits IRF-1 mRNA induction and prevents IL-1 beta-induced nitric oxide synthase expression in pancreatic beta cells.
    Biochem Biophys Res Commun. 1995 Oct 13;215(2):524-30 PMID: 7487987
  11. The inducible nitric oxide synthase gene, Nos2, maps to mouse chromosome 11.
    Mamm Genome. 1994 May;5(5):318-20 PMID: 7521235
  12. What are the types and cellular sources of free radicals in the pathogenesis of type 1 (insulin-dependent) diabetes mellitus?
    Diabetologia. 1993 May;36(5):470-1 PMID: 7686111
  13. Nitric oxide synthase structure and mechanism.
    J Biol Chem. 1993 Jun 15;268(17):12231-4 PMID: 7685338
  14. Biochemical and molecular actions of interleukin-1 on pancreatic beta-cells.
    Autoimmunity. 1991;10(3):241-53 PMID: 1836745
  15. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation.
    Cell. 1995 Jan 27;80(2):179-85 PMID: 7834738
  16. The lethal effects of cytokine-induced nitric oxide on cardiac myocytes are blocked by nitric oxide synthase antagonism or transforming growth factor beta.
    J Clin Invest. 1995 Feb;95(2):677-85 PMID: 7532189
  17. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene.
    J Biol Chem. 1993 Aug 15;268(23):17478-88 PMID: 7688726
  18. JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain.
    Cell. 1994 Mar 25;76(6):1025-37 PMID: 8137421
  19. Cytokines suppress human islet function irrespective of their effects on nitric oxide generation.
    J Clin Invest. 1994 May;93(5):1968-74 PMID: 7514190
  20. Intraislet release of interleukin 1 inhibits beta cell function by inducing beta cell expression of inducible nitric oxide synthase.
    J Exp Med. 1995 Feb 1;181(2):559-68 PMID: 7530759
  21. Macrophage synthesis of nitrite, nitrate, and N-nitrosamines: precursors and role of the respiratory burst.
    Proc Natl Acad Sci U S A. 1987 Sep;84(18):6369-73 PMID: 2819872
  22. Interleukin-1-induced activation of a protein kinase co-precipitating with the type I interleukin-1 receptor in T cells.
    Eur J Immunol. 1994 Jul;24(7):1566-71 PMID: 8026518
  23. Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase.
    Cell. 1995 May 19;81(4):641-50 PMID: 7538909
  24. Repair of pancreatic beta-cells. A relevant phenomenon in early IDDM?
    Diabetes. 1993 Oct;42(10):1383-91 PMID: 8375580
  25. 1,2-Diacylglycerols but not phorbol esters stimulate sphingomyelin hydrolysis in GH3 pituitary cells.
    J Biol Chem. 1987 Dec 15;262(35):16759-62 PMID: 3479432
  26. Promoter of the mouse gene encoding calcium-independent nitric oxide synthase confers inducibility by interferon gamma and bacterial lipopolysaccharide.
    J Exp Med. 1993 Jun 1;177(6):1779-84 PMID: 7684434
  27. Three members of the nitric oxide synthase II gene family (NOS2A, NOS2B, and NOS2C) colocalize to human chromosome 17.
    Genomics. 1995 Jun 10;27(3):526-30 PMID: 7558036
  28. Tyrosine kinase involvement in IL-1 beta-induced expression of iNOS by beta-cells purified from islets of Langerhans.
    Am J Physiol. 1994 Jul;267(1 Pt 1):C48-54 PMID: 7519400
  29. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase.
    Nature. 1991 Jun 27;351(6329):714-8 PMID: 1712077
  30. The high-output nitric oxide pathway: role and regulation.
    J Leukoc Biol. 1994 Nov;56(5):576-82 PMID: 7525816
  31. Nitric oxide donors decrease the function and survival of human pancreatic islets.
    Mol Cell Endocrinol. 1996 Apr 19;118(1-2):71-83 PMID: 8735593
  32. Interleukin-1 beta-induced ceramide and diacylglycerol generation may lead to activation of the c-Jun NH2-terminal kinase and the transcription factor ATF2 in the insulin-producing cell line RINm5F.
    J Biol Chem. 1996 Apr 5;271(14):8307-12 PMID: 8626526
  33. Transforming growth factor-beta inhibits the cytokine-mediated expression of the inducible nitric oxide synthase mRNA in human retinal pigment epithelial cells.
    Biochem Biophys Res Commun. 1995 Oct 4;215(1):386-93 PMID: 7575617
  34. Interleukin-1 beta induces the expression of an isoform of nitric oxide synthase in insulin-producing cells, which is similar to that observed in activated macrophages.
    FEBS Lett. 1992 Aug 24;308(3):249-52 PMID: 1380466
  35. Regional localization of the gene coding for human brain nitric oxide synthase (NOS1) to 12q24.2-->24.31 by fluorescent in situ hybridization.
    Cytogenet Cell Genet. 1993;64(1):62-3 PMID: 7685260
  36. Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin.
    J Exp Med. 1992 Jul 1;176(1):261-4 PMID: 1377225
  37. Interleukin-1 beta increases the activity of superoxide dismutase in rat pancreatic islets.
    Endocrinology. 1992 May;130(5):2851-7 PMID: 1533363
  38. Endothelial nitric oxide synthase: molecular cloning and characterization of a distinct constitutive enzyme isoform.
    Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6348-52 PMID: 1378626
  39. IL-1 beta induces the coexpression of both nitric oxide synthase and cyclooxygenase by islets of Langerhans: activation of cyclooxygenase by nitric oxide.
    Biochemistry. 1993 Dec 21;32(50):13767-70 PMID: 7505613
  40. Nitric oxide production in islets from nonobese diabetic mice: aminoguanidine-sensitive and -resistant stages in the immunological diabetic process.
    Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8992-5 PMID: 7692442
  41. A hypoxia-responsive element mediates a novel pathway of activation of the inducible nitric oxide synthase promoter.
    J Exp Med. 1995 Dec 1;182(6):1683-93 PMID: 7500013
  42. Localization and characterization of interleukin-1 receptors in the islets of Langerhans from control and nonobese diabetic mice.
    Endocrinology. 1995 Feb;136(2):609-13 PMID: 7835294
  43. IL-6DBP, a nuclear protein involved in interleukin-6 signal transduction, defines a new family of leucine zipper proteins related to C/EBP.
    Cell. 1990 Nov 2;63(3):643-53 PMID: 2171780
  44. Rapid proteolysis of I kappa B-alpha is necessary for activation of transcription factor NF-kappa B.
    Nature. 1993 Sep 9;365(6442):182-5 PMID: 8371761
  45. Insulin-dependent diabetes mellitus as a beta-cell targeted disease of immunoregulation.
    J Autoimmun. 1995 Aug;8(4):439-63 PMID: 7492343
  46. Endogenous nitric oxide induced by interleukin-1 beta in rat islets of Langerhans and HIT-T15 cells causes significant DNA damage as measured by the 'comet' assay.
    FEBS Lett. 1993 Nov 1;333(3):291-5 PMID: 8224196
  47. Dissociation between interleukin-1 beta-induced expression of mRNA for superoxide dismutase and nitric oxide synthase in insulin-producing cells.
    Biochem Biophys Res Commun. 1994 Sep 30;203(3):1542-7 PMID: 7524486
  48. On the expression of nitric oxide synthase by human macrophages. Why no NO?
    J Leukoc Biol. 1995 Dec;58(6):643-9 PMID: 7499961
  49. Major species differences between humans and rodents in the susceptibility to pancreatic beta-cell injury.
    Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9253-6 PMID: 7937750
  50. Heat shock protein induction in rat pancreatic islets by recombinant human interleukin 1 beta.
    Diabetologia. 1991 Mar;34(3):150-6 PMID: 1884886
  51. Interleukin-1 beta-induced nitric oxide synthase expression by rat pancreatic beta-cells: evidence for the involvement of nuclear factor kappa B in the signaling mechanism.
    Endocrinology. 1995 Nov;136(11):4790-5 PMID: 7588208
  52. Parallel induction of heme oxygenase-1 and chemoprotective phase 2 enzymes by electrophiles and antioxidants: regulation by upstream antioxidant-responsive elements (ARE).
    Mol Med. 1995 Nov;1(7):827-37 PMID: 8612205
  53. The cytokine responsive vascular smooth muscle cell enhancer of inducible nitric oxide synthase. Activation by nuclear factor-kappa B.
    J Biol Chem. 1995 Dec 8;270(49):29541-7 PMID: 7493996
  54. Nicotinamide and dexamethasone inhibit interleukin-1-induced nitric oxide production by RINm5F cells without decreasing messenger ribonucleic acid expression for nitric oxide synthase.
    Endocrinology. 1993 Oct;133(4):1739-43 PMID: 7691579
  55. Molecular genetic analysis of the duplication of human inducible nitric oxide synthase (NOS2) sequences.
    Biochem Biophys Res Commun. 1995 Jul 17;212(2):466-72 PMID: 7542877
  56. Interleukin-1 enhances pancreatic islet arachidonic acid 12-lipoxygenase product generation by increasing substrate availability through a nitric oxide-dependent mechanism.
    J Biol Chem. 1996 Jan 12;271(2):1029-42 PMID: 8557627
  57. Macrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon gamma and lipopolysaccharide.
    Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9730-4 PMID: 7692452
  58. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production.
    J Immunol. 1988 Oct 1;141(7):2407-12 PMID: 3139757
  59. Influence of protease on inhibitory and stimulatory effects of interleukin 1 beta on beta-cell function.
    Diabetes. 1991 Feb;40(2):290-4 PMID: 1991576
  60. Coinduction of nitric oxide synthase, argininosuccinate synthetase, and argininosuccinate lyase in lipopolysaccharide-treated rats. RNA blot, immunoblot, and immunohistochemical analyses.
    J Biol Chem. 1996 Feb 2;271(5):2658-62 PMID: 8576237
  61. Tyrosine kinase inhibitors, genistein and herbimycin A, do not block interleukin-1 beta-induced activation of NF-kappa B in rat mesangial cells.
    Biochem Biophys Res Commun. 1996 Jan 26;218(3):808-12 PMID: 8579596
  62. Secretory products of macrophages.
    J Clin Invest. 1987 Feb;79(2):319-26 PMID: 3543052
  63. Cloning, characterization, and expression of a cDNA encoding an inducible nitric oxide synthase from the human chondrocyte.
    Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11419-23 PMID: 7504305
  64. Interleukin-1 induces rapid and transient expression of the c-fos proto-oncogene in isolated pancreatic islets and in purified beta-cells.
    FEBS Lett. 1990 Jun 18;266(1-2):33-6 PMID: 2114318
  65. Interleukin-1 beta-induced nitric oxide production in isolated rat pancreatic islets requires gene transcription and may lead to inhibition of the Krebs cycle enzyme aconitase.
    Endocrinology. 1991 Dec;129(6):3167-73 PMID: 1720090
  66. Structural diversity in the 5'-untranslated region of cytokine-stimulated human inducible nitric oxide synthase mRNA.
    J Biol Chem. 1995 May 5;270(18):10625-30 PMID: 7537735
  67. Ceramide activates the stress-activated protein kinases.
    J Biol Chem. 1995 Sep 29;270(39):22689-92 PMID: 7559390
  68. Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells.
    J Exp Med. 1992 May 1;175(5):1181-94 PMID: 1314883
  69. Argininosuccinate synthetase mRNA and activity are induced by immunostimulants in vascular smooth muscle. Role in the regeneration or arginine for nitric oxide synthesis.
    J Biol Chem. 1994 Apr 1;269(13):9405-8 PMID: 7511585
  70. Differential expression and induction of mRNAs encoding two inducible nitric oxide synthases in rat kidney.
    Kidney Int. 1994 Sep;46(3):653-65 PMID: 7527874
  71. New insights into the regulation of inducible nitric oxide synthesis.
    Am J Physiol. 1994 Jun;266(6 Pt 1):E829-39 PMID: 8023911
  72. Interleukin-1 stimulates the expression of type I and type II interleukin-1 receptors in the rat insulinoma cell line Rinm5F; sequencing a rat type II interleukin-1 receptor cDNA.
    Eur Cytokine Netw. 1994 May-Jun;5(3):319-30 PMID: 7524717
  73. N omega-hydroxyl-L-arginine, an intermediate in the L-arginine to nitric oxide pathway, is a strong inhibitor of liver and macrophage arginase.
    Biochem Biophys Res Commun. 1994 Sep 30;203(3):1614-21 PMID: 7945311
  74. Superoxide and peroxynitrite inactivate aconitases, but nitric oxide does not.
    J Biol Chem. 1994 Nov 25;269(47):29405-8 PMID: 7961919
  75. Differences in the expression of heat-shock proteins and antioxidant enzymes between human and rodent pancreatic islets: implications for the pathogenesis of insulin-dependent diabetes mellitus.
    Mol Med. 1995 Nov;1(7):806-20 PMID: 8612203
  76. Molecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophage cell line.
    J Biol Chem. 1992 Mar 25;267(9):6370-4 PMID: 1372907
  77. Strain-dependent differences in sensitivity of rat beta-cells to interleukin 1 beta in vitro and in vivo: association with islet nitric oxide synthesis.
    Diabetes. 1996 Jun;45(6):771-8 PMID: 8635652
  78. Cloned and expressed macrophage nitric oxide synthase contrasts with the brain enzyme.
    Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6711-5 PMID: 1379716
  79. Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes.
    Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3491-5 PMID: 7682706
  80. Mechanisms of suppression of macrophage nitric oxide release by transforming growth factor beta.
    J Exp Med. 1993 Aug 1;178(2):605-13 PMID: 7688028
  81. Protein-binding sites in Ig gene enhancers determine transcriptional activity and inducibility.
    Science. 1987 Jun 19;236(4808):1573-7 PMID: 3109035
  82. Role of receptor binding and gene transcription for both the stimulatory and inhibitory effects of interleukin-1 in pancreatic beta-cells.
    Autoimmunity. 1992;12(2):127-33 PMID: 1535517
  83. Liposomal delivery of purified heat shock protein hsp70 into rat pancreatic islets as protection against interleukin 1 beta-induced impaired beta-cell function.
    Diabetes. 1991 Nov;40(11):1418-22 PMID: 1936603
  84. Interleukin-1 beta increases the biosynthesis of the heat shock protein hsp70 and selectively decreases the biosynthesis of five proteins in rat pancreatic islets.
    Autoimmunity. 1991;9(1):33-40 PMID: 1669845
  85. Molecular cloning and characterization of human endothelial nitric oxide synthase.
    FEBS Lett. 1992 Aug 3;307(3):287-93 PMID: 1379542
  86. Transactivation by NF-IL6/LAP is enhanced by phosphorylation of its activation domain.
    Nature. 1993 Aug 5;364(6437):544-7 PMID: 8336793
  87. Cytokines activate the nuclear factor kappa B (NF-kappa B) and induce nitric oxide production in human pancreatic islets.
    FEBS Lett. 1996 Apr 29;385(1-2):4-6 PMID: 8641463
  88. Nitric oxide activates cyclooxygenase enzymes.
    Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7240-4 PMID: 7688473
  89. Effects of protein kinase C activation on the regulation of the stimulus-secretion coupling in pancreatic beta-cells.
    Biochem J. 1989 Nov 15;264(1):207-15 PMID: 2690820
  90. Transcriptional regulation of human inducible nitric oxide synthase (NOS2) gene by cytokines: initial analysis of the human NOS2 promoter.
    Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1054-9 PMID: 8577713
  91. Localization of the human gene for inducible nitric oxide synthase (NOS2) to chromosome 17q11.2-q12.
    Genomics. 1994 Jan 1;19(1):183-5 PMID: 7514565
  92. Islet cell DNA is a target of inflammatory attack by nitric oxide.
    Diabetes. 1993 Mar;42(3):496-500 PMID: 8432420
  93. A role for tyrosine kinase activation in interleukin-1 beta induced nitric oxide production in the insulin producing cell line RINm-5F.
    Biosci Rep. 1994 Feb;14(1):43-50 PMID: 8032008
  94. Promoter analysis of human inducible nitric oxide synthase gene associated with cardiovascular homeostasis.
    Biochem Biophys Res Commun. 1994 Apr 29;200(2):802-7 PMID: 7513995
  95. The simultaneous generation of superoxide and nitric oxide can initiate lipid peroxidation in human low density lipoprotein.
    Free Radic Res Commun. 1992;17(1):9-20 PMID: 1332919
  96. Interleukin-1 beta induces the expression of hsp70, heme oxygenase and Mn-SOD in FACS-purified rat islet beta-cells, but not in alpha-cells.
    Immunol Lett. 1995 Dec;48(2):145-8 PMID: 8719114
  97. Nitric oxide: a physiologic messenger.
    Ann Intern Med. 1994 Feb 1;120(3):227-37 PMID: 8273987
  98. Coinduction of nitric oxide synthase and argininosuccinate synthetase in a murine macrophage cell line. Implications for regulation of nitric oxide production.
    J Biol Chem. 1994 Jan 14;269(2):1257-61 PMID: 7507106
  99. IRAK: a kinase associated with the interleukin-1 receptor.
    Science. 1996 Feb 23;271(5252):1128-31 PMID: 8599092
  100. Arginine metabolism in wounds.
    Am J Physiol. 1988 Apr;254(4 Pt 1):E459-67 PMID: 3354662
  101. Studies on the molecular regulation of the inducible form of nitric oxide synthase (iNOS) in insulin-producing cells.
    Mol Cell Endocrinol. 1994 Dec;106(1-2):151-5 PMID: 7534733
  102. Mapping of the genes encoding human inducible and endothelial nitric oxide synthase (NOS2 and NOS3) to the pericentric region of chromosome 17 and to chromosome 7, respectively.
    Genomics. 1994 May 15;21(2):419-22 PMID: 7522210
  103. Inducible nitric oxide synthase from a rat alveolar macrophage cell line is inhibited by nitric oxide.
    J Immunol. 1993 Dec 1;151(11):6329-37 PMID: 7504017
  104. Heat shock induces resistance in rat pancreatic islet cells against nitric oxide, oxygen radicals and streptozotocin toxicity in vitro.
    J Clin Invest. 1995 Jun;95(6):2840-5 PMID: 7769124
  105. Expression of the citrulline-nitric oxide cycle in rodent and human pancreatic beta-cells: induction of argininosuccinate synthetase by cytokines.
    Endocrinology. 1995 Aug;136(8):3200-6 PMID: 7628352
  106. Succinic acid monomethyl ester protects rat pancreatic islet secretory potential against interleukin-1 beta (IL-1 beta) without affecting glutamate decarboxylase expression or nitric oxide production.
    FEBS Lett. 1994 Jan 17;337(3):298-302 PMID: 8293819
  107. Increased intracellular Ca2+ selectively suppresses IL-1-induced NO production by reducing iNOS mRNA stability.
    J Cell Biol. 1995 Jun;129(6):1651-7 PMID: 7540612
  108. Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun.
    Nature. 1994 Dec 22-29;372(6508):794-8 PMID: 7997269
  109. Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation.
    J Immunol. 1983 Apr;130(4):1910-7 PMID: 6833755
  110. Role of ceramide-activated protein phosphatase in ceramide-mediated signal transduction.
    J Biol Chem. 1994 Jul 29;269(30):19605-9 PMID: 8034729
  111. Insulin-secreting beta-cells possess specific receptors for interleukin-1 beta.
    FEBS Lett. 1990 Feb 12;261(1):97-100 PMID: 2137789
  112. Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle.
    FEBS Lett. 1993 Jan 25;316(2):175-80 PMID: 7678401
  113. The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway.
    Cell. 1995 Jun 30;81(7):1137-46 PMID: 7600581
  114. The L-arginine-nitric oxide pathway.
    N Engl J Med. 1993 Dec 30;329(27):2002-12 PMID: 7504210
  115. Altered immune responses in mice lacking inducible nitric oxide synthase.
    Nature. 1995 Jun 1;375(6530):408-11 PMID: 7539113
  116. Nicotinamide decreases nitric oxide production and partially protects human pancreatic islets against the suppressive effects of combinations of cytokines.
    Autoimmunity. 1994;19(3):193-8 PMID: 7605871
  117. Induction of nitric oxide synthase mRNA expression. Suppression by exogenous nitric oxide.
    J Biol Chem. 1995 Nov 10;270(45):26731-3 PMID: 7592903
  118. A natural interleukin 1 (IL-1) inhibitor counteracts the inhibitory effect of IL-1 on insulin production in cultured rat pancreatic islets.
    J Autoimmun. 1989 Apr;2(2):163-71 PMID: 2527507
  119. Interleukin-1 beta-induced stimulation of insulin release in mouse pancreatic islets is related to diacylglycerol production and protein kinase C activation.
    Mol Cell Endocrinol. 1995 Jun;111(2):159-65 PMID: 7556877
  120. A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins.
    Cell. 1994 Sep 23;78(6):1027-37 PMID: 7923353
  121. Induction and stabilization of I kappa B alpha by nitric oxide mediates inhibition of NF-kappa B.
    J Biol Chem. 1995 Jun 9;270(23 ):14214-9 PMID: 7775482
  122. NF-kappa B activation by interleukin-1 (IL-1) requires an IL-1 receptor-associated protein kinase activity.
    J Biol Chem. 1995 Jul 14;270(28):16514-7 PMID: 7622454
  123. Interleukin-1-induced expression of nitric oxide synthase in insulin-producing cells is preceded by c-fos induction and depends on gene transcription and protein synthesis.
    FEBS Lett. 1993 Feb 8;317(1-2):62-6 PMID: 7679081
  124. Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase.
    J Biol Chem. 1992 Jul 25;267(21):14519-22 PMID: 1378832
  125. Cloning and characterization of inducible nitric oxide synthase from mouse macrophages.
    Science. 1992 Apr 10;256(5054):225-8 PMID: 1373522
  126. An interleukin-1 receptor antagonist protein protects insulin-producing beta cells against suppressive effects of interleukin-1 beta.
    Diabetologia. 1991 Jun;34(6):445-8 PMID: 1832112
  127. Two-dimensional gel electrophoresis of rat islet proteins. Interleukin 1 beta-induced changes in protein expression are reduced by L-arginine depletion and nicotinamide.
    Diabetes. 1995 Apr;44(4):400-7 PMID: 7698507
  128. Role of endothelium-derived nitric oxide in the regulation of blood pressure.
    Proc Natl Acad Sci U S A. 1989 May;86(9):3375-8 PMID: 2497467
  129. The inducible transcription factor NF-kappa B: structure-function relationship of its protein subunits.
    Biochem J. 1993 Mar 1;290 ( Pt 2):297-308 PMID: 8452515
  130. Mice lacking inducible nitric oxide synthase are not resistant to lipopolysaccharide-induced death.
    Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10688-92 PMID: 7479866
  131. Functional characteristics of rat pancreatic islets maintained in culture after exposure to human interleukin 1.
    Diabetes. 1988 Jul;37(7):916-9 PMID: 3290009
  132. Interleukin-10 stimulates rat pancreatic islets in vitro, but fails to protect against interleukin-1.
    Biochem Biophys Res Commun. 1993 Sep 15;195(2):859-65 PMID: 8373422
  133. Interleukin-10 (IL-10) inhibits the induction of nitric oxide synthase by interferon-gamma in murine macrophages.
    Biochem Biophys Res Commun. 1992 Feb 14;182(3):1155-9 PMID: 1371674
  134. Aconitase is readily inactivated by peroxynitrite, but not by its precursor, nitric oxide.
    J Biol Chem. 1994 Nov 25;269(47):29409-15 PMID: 7961920
  135. Human pancreatic islet beta-cell destruction by cytokines is independent of nitric oxide production.
    J Clin Endocrinol Metab. 1994 Oct;79(4):1058-62 PMID: 7962274
  136. Nitric oxide mediates cytokine-induced inhibition of insulin secretion by human islets of Langerhans.
    Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1731-5 PMID: 8383325
  137. Nitric oxide synthases: properties and catalytic mechanism.
    Annu Rev Physiol. 1995;57:707-36 PMID: 7539994
  138. Cloning and expression of cytokine-inducible nitric oxide synthase cDNA from rat islets of Langerhans.
    Diabetes. 1995 Jul;44(7):753-8 PMID: 7540573
  139. Co-induction of arginase and nitric oxide synthase in murine macrophages activated by lipopolysaccharide.
    Biochem Biophys Res Commun. 1995 May 25;210(3):1009-16 PMID: 7539253
  140. Nitric oxide: first in a new class of neurotransmitters.
    Science. 1992 Jul 24;257(5069):494-6 PMID: 1353273
  141. Messenger RNA degradation in eukaryotes.
    Cell. 1993 Aug 13;74(3):413-21 PMID: 7688664
  142. Differential interleukin-1 receptor antagonism on pancreatic beta and alpha cells. Studies in rodent and human islets and in normal rats.
    Diabetologia. 1993 Aug;36(8):759-66 PMID: 8405744
  143. A possible novel pathway of regulation by murine T helper type-2 (Th2) cells of a Th1 cell activity via the modulation of the induction of nitric oxide synthase on macrophages.
    Eur J Immunol. 1991 Oct;21(10):2489-94 PMID: 1717284
  144. Transcription factor ATF2 regulation by the JNK signal transduction pathway.
    Science. 1995 Jan 20;267(5196):389-93 PMID: 7824938
  145. Requirement for transcription factor IRF-1 in NO synthase induction in macrophages.
    Science. 1994 Mar 18;263(5153):1612-5 PMID: 7510419
  146. Recombinant human transforming growth factor beta does not inhibit the effects of interleukin-1 beta on pancreatic islet cells.
    J Interferon Cytokine Res. 1995 Dec;15(12):1075-81 PMID: 8746789
  147. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation.
    Biochim Biophys Acta. 1991 Dec 10;1072(2-3):129-57 PMID: 1751545
  148. Cytokine and free radicals as effector molecules in the destruction of pancreatic beta cells.
    Curr Top Microbiol Immunol. 1990;164:169-93 PMID: 2073784
  149. TNF activates NF-kappa B by phosphatidylcholine-specific phospholipase C-induced "acidic" sphingomyelin breakdown.
    Cell. 1992 Nov 27;71(5):765-76 PMID: 1330325
  150. Nitric oxide synthase: expression and expressional control of the three isoforms.
    Naunyn Schmiedebergs Arch Pharmacol. 1995 Oct;352(4):351-64 PMID: 8532063
  151. Inhibition of insulin secretion by interleukin-1 beta and tumour necrosis factor-alpha via an L-arginine-dependent nitric oxide generating mechanism.
    FEBS Lett. 1990 Dec 10;276(1-2):42-4 PMID: 2265709
  152. Interleukin-1 beta regulates the expression of a leukocyte type of 12-lipoxygenase in rat islets and RIN m5F cells.
    Endocrinology. 1995 Dec;136(12):5736-44 PMID: 7588331
  153. Calmodulin is a subunit of nitric oxide synthase from macrophages.
    J Exp Med. 1992 Aug 1;176(2):599-604 PMID: 1380065
  154. Modulation of inducible nitric oxide synthase in RINm5F cells.
    Cell Signal. 1994 Jan;6(1):17-24 PMID: 7516691
  155. Natural resistance and nitric oxide.
    Cell. 1995 Sep 22;82(6):873-6 PMID: 7553846
  156. Interleukin-1 beta-induced nitric oxide production from isolated rat islets is modulated by D-glucose and 3-isobutyl-1-methyl xanthine.
    Eur J Endocrinol. 1996 Feb;134(2):251-9 PMID: 8630528
  157. Interleukin-1 beta induced activation of NF-kappa B in insulin producing RINm5F cells is prevented by the protease inhibitor N alpha-p-tosyl-L-lysine chloromethylketone.
    Biochem Biophys Res Commun. 1994 Aug 30;203(1):149-55 PMID: 8074648
  158. TNF-alpha and IFN-gamma potentiate the deleterious effects of IL-1 beta on mouse pancreatic islets mainly via generation of nitric oxide.
    Cytokine. 1994 Jul;6(4):399-406 PMID: 7948748
  159. Type 1 (insulin-dependent) diabetes mellitus and nitric oxide.
    Diabetologia. 1992 Aug;35(8):796-7 PMID: 1387373
  160. Nitric oxide limits transcriptional induction of nitric oxide synthase in CNS glial cells.
    Biochem Biophys Res Commun. 1994 Jun 15;201(2):762-8 PMID: 7516158
  161. Pyrrolidine dithiocarbamate prevents IL-1-induced nitric oxide synthase mRNA, but not superoxide dismutase mRNA, in insulin producing cells.
    Biochem Biophys Res Commun. 1995 May 25;210(3):816-22 PMID: 7539260
  162. Inducible nitric-oxide-synthase mRNA is transiently expressed and destroyed by a cycloheximide-sensitive process.
    Eur J Biochem. 1994 Jan 15;219(1-2):563-9 PMID: 7508391
Article Info
Journal
Diabetologia
Abbr.
Diabetologia
ISSN
0012-186X
DOI
10.1007/BF00403906
Published
1996-08-00
Pages
875-90
Language
English
Region
Germany
NLM ID
0006777
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00403906 View journal details
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