Histone deacetylase (HDAC) inhibition as a novel treatment for diabetes mellitus

Molecular Medicine

Volumn 17, Issue 5-6, 2011, Pages 378-390

  Christensen, Dan P ^a   Dahllöf, Mattias ^a   Lundh, Morten ^a   Rasmussen, Daniel N ^a   Nielsen, Mette D ^a   Billestrup, Nils ^a   Grunnet, Lars G ^a   Mandrup Poulsen, Thomas ^a,b,c,d  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b HAGEDORN RESEARCH INSTITUTE   (Denmark)

^c KAROLINSKA INSTITUTE   (Sweden)

^d UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOOXYGENASE 2; GAMMA INTERFERON; GIVINOSTAT; GLUCOSE TRANSPORTER 4; HISTONE ACETYLTRANSFERASE; HISTONE ACETYLTRANSFERASE PCAF; HISTONE DEACETYLASE; HISTONE DEACETYLASE 2; HISTONE DEACETYLASE 3; HISTONE DEACETYLASE INHIBITOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INSULIN RECEPTOR SUBSTRATE; INTERLEUKIN 1BETA; NEUROGENIC DIFFERENTIATION FACTOR; NEUROGENIN 3; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; SARCOPLASMIC RETICULUM CALCIUM TRANSPORTING ADENOSINE TRIPHOSPHATASE; STAT1 PROTEIN; TRANSCRIPTION FACTOR MAFA; TRANSCRIPTION FACTOR PDX 1; TRANSCRIPTION FACTOR SIN3A; TRANSCRIPTION FACTOR SOX3; TRANSCRIPTION FACTOR SOX6; TRICHOSTATIN A; VALPROIC ACID; VORINOSTAT;

ACETYLATION; ADAPTIVE IMMUNITY; ANTIINFLAMMATORY ACTIVITY; ARTICLE; BIPOLAR DISORDER; CELL CYCLE REGULATION; CELL DEATH; CELL DESTRUCTION; CELL DIFFERENTIATION; CELL MATURATION; CELL PROTECTION; CHROMATIN ASSEMBLY AND DISASSEMBLY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DEACETYLATION; DIABETES MELLITUS; DNA METHYLATION; DRUG MECHANISM; ENDOCRINE CELL; ENDOPLASMIC RETICULUM STRESS; ENZYME ACTIVITY; ENZYME INHIBITION; EPIGENETICS; EPILEPSY; GENETIC ASSOCIATION; HUMAN; HYPERINSULINEMIA; IMMUNOMODULATION; INNATE IMMUNITY; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN RELEASE; INSULIN RESISTANCE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS CELL; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; SIDE EFFECT; TRANSCRIPTION REGULATION; WEIGHT GAIN;

ANIMALS; ANTI-INFLAMMATORY AGENTS; DIABETES MELLITUS; HISTONE DEACETYLASE INHIBITORS; HISTONE DEACETYLASES; HUMANS; INTERLEUKIN-1BETA;

EID: 79957944601     PISSN: 10761551     EISSN: None     Source Type: Journal    
DOI: 10.2119/molmed.2011.00021     Document Type: Article

References (158)

1. Raj SM, et al. (2009) No association of multiple type 2 diabetes loci with type 1 diabetes. Dia-betologia 52:2109-2116.
2. Barrett JC, et al. (2009) Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat. Genet. 41:703-707.
3. Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG. (2009) Analysis of islet inflammation in human type 1 diabetes. Clin. Exp. Immunol. 155:173-181.
4. Prokopenko I, McCarthy MI, Lindgren CM. (2008) Type 2 diabetes: new genes, new understanding. Trends Genet. 24:613-621.
5. Wilkin TJ. (2007) Changing perspectives in diabetes: their impact on its classification. Diabetolo-gia 50:1587-1592.
6. Butler AE, et al. (2003) Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 52:102-110.
7. Sakuraba H, et al. (2002) Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese type II diabetic patients. Diabetologia 45:85-96.
8. Yoon KH, et al. (2003) Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea. J. Clin. Endocrinol. Metab. 88:2300-2308.
9. Ehses JA, Ellingsgaard H, Boni-Schnetzler M, Donath MY. (2009) Pancreatic islet inflammation in type 2 diabetes: from alpha and beta cell compensation to dysfunction. Arch. Physiol. Biochem. 115:240-247.
10. Masters SL, et al. (2010) Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1beta in type 2 diabetes. Nat. Immunol. 11:897-904.
11. Mandrup-Poulsen T. (2010) IAPP boosts islet macrophage IL-1 in type 2 diabetes. Nat. Immunol. 11:881-883.
12. Donath MY, Storling J, Berchtold LA, Billestrup N, Mandrup-Poulsen T. (2008) Cytokines and beta-cell biology: from concept to clinical translation. Endocr. Rev. 29:334-350.
13. Mandrup-Poulsen T. (1996) The role of inter-leukin-1 in the pathogenesis of IDDM. Diabetolo-gia 39:1005-1029.
14. Stienstra R, et al. (2010) The inflammasome-medi-ated caspase-1 activation controls adipocyte differentiation and insulin sensitivity. Cell Metab. 12:593-605.
15. Maedler K, et al. (2002) Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J. Clin. Invest. 110:851-860.
16. Maedler K, et al. (2004) Leptin modulates beta cell expression of IL-1 receptor antagonist and release of IL-1beta in human islets. Proc. Natl. Acad. Sci. U. S. A. 101:8138-8143.
17. Sauter NS, Schulthess FT, Galasso R, Castellani LW, Maedler K. (2008) The antiinflammatory cy-tokine interleukin-1 receptor antagonist protects from high-fat diet-induced hyperglycemia. Endocrinology 149:2208-2218.
18. Spranger J, et al. (2003) Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 52:812-817.
19. Larsen CM, et al. (2007) Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N. Engl. J. Med. 356:1517-1526.
20. Larsen CM, et al. (2009) Sustained effects of inter-leukin-1 receptor antagonist treatment in type 2 diabetes. Diabetes Care 32:1663-1668.
21. Halili MA, Andrews MR, Sweet MJ, Fairlie DP. (2009) Histone deacetylase inhibitors in inflammatory disease. Curr. Top. Med. Chem. 9:309-319.
22. Gregoretti IV, Lee YM, Goodson HV. (2004) Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J. Mol. Biol. 338:17-31.
23. Choudhary C, et al. (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325:834-840.
24. Mankan AK, Lawless MW, Gray SG, Kelleher D, McManus R. (2009) NF-kappaB regulation: the nuclear response. J. Cell. Mol. Med. 13:631-643.
25. Giannoukakis N, Rudert WA, Trucco M, Robbins PD. (2000) Protection of human islets from the effects of interleukin-1beta by adenoviral gene transfer of an Ikappa B repressor. J. Biol. Chem. 275:36509-36513.
26. Heimberg H, et al. (2001) Inhibition of cytokine-induced NF-kappaB activation by adenovirus-mediated expression of a NF-kappaB super-repressor prevents beta-cell apoptosis. Diabetes 50:2219-2224.
27. Larsen L, et al. (2007) Inhibition of histone deacetylases prevents cytokine-induced toxicity in beta cells. Diabetologia 50:779-789.
28. Lee HB, Noh H, Seo JY, Yu MR, Ha H. (2007) His-tone deacetylase inhibitors: a novel class of therapeutic agents in diabetic nephropathy. Kidney Int. Suppl. S61-S66.
29. Villeneuve LM, Natarajan R. (2010) The role of epigenetics in the pathology of diabetic complications. Am. J. Physiol. Renal Physiol. 299:F14-F25.
30. Crosson CE, Mani SK, Husain S, Alsarraf O, Menick DR. (2010) Inhibition of histone deacety-lase protects the retina from ischemic injury. Invest. Ophthalmol. Vis. Sci. 51:3639-3645.
31. Bonnefond A, Froguel P, Vaxillaire M. (2010) The emerging genetics of type 2 diabetes. Trends Mol. Med. 16:407-416.
32. Pociot F, et al. (2010) Genetics of type 1 diabetes: what's next? Diabetes 59:1561-1571.
33. Nerup J, Pociot F. (2001) A genomewide scan for type 1-diabetes susceptibility in Scandinavian families: identification of new loci with evidence of interactions. Am. J. Hum. Genet. 69:1301-1313.
34. Xiang K, et al. (2004) Genome-wide search for type 2 diabetes/impaired glucose homeostasis susceptibility genes in the Chinese: significant linkage to chromosome 6q21-q23 and chromosome 1q21-q24. Diabetes 53:228-234.
35. Redondo MJ, Fain PR, Eisenbarth GS. (2001) Genetics of type 1A diabetes. Recent Prog. Horm. Res. 56:69-89.
36. Poulsen P, Kyvik KO, Vaag A, Beck-Nielsen H. (1999) Heritability of type II (non-insulin-dependent) diabetes mellitus and abnormal glucose tolerance: a population-based twin study. Dia-betologia 42:139-145.
37. Pinney SE, Simmons RA. (2010) Epigenetic mechanisms in the development of type 2 diabetes. Trends Endocrinol. Metab. 21:223-229.
38. Park JH, Stoffers DA, Nicholls RD, Simmons RA. (2008) Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1. J. Clin. Invest. 118:2316-2324.
39. Raychaudhuri N, Raychaudhuri S, Thamotharan M, Devaskar SU. (2008) Histone code modifications repress glucose transporter 4 expression in the intrauterine growth-restricted offspring. J. Biol. Chem. 283:13611-13626.
40. Kim SJ, Nian C, McIntosh CH. (2009) Glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 modulate beta-cell chro-matin structure. J. Biol. Chem. 284:12896-12904.
41. Gray SG, De Meyts P. (2005) Role of histone and transcription factor acetylation in diabetes patho-genesis. Diabetes Metab. Res. Rev. 21:416-433.
42. Camelo S, et al. (2005) Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune en-cephalomyelitis. J. Neuroimmunol. 164:10-21.
43. Lin HS, et al. (2007) Anti-rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen-induced arthritis in rodents. Br. J. Pharmacol. 150:862-872.
44. Suuronen T, Huuskonen J, Pihlaja R, Kyrylenko S, Salminen A. (2003) Regulation of microglial inflammatory response by histone deacetylase inhibitors. J. Neurochem. 87:407-416.
45. Suh HS, Choi S, Khattar P, Choi N, Lee SC. (2010) Histone deacetylase inhibitors suppress the expression of inflammatory and innate immune response genes in human microglia and astrocytes. J. Neuroimmune Pharmacol. 5:521-532.
46. Miao F, Gonzalo IG, Lanting L, Natarajan R. (2004) In vivo chromatin remodeling events leading to inflammatory gene transcription under diabetic conditions. J. Biol. Chem. 279:18091-18097.
47. Shanmugam N, Reddy MA, Guha M, Natarajan R. (2003) High glucose-induced expression of proinflammatory cytokine and chemokine genes in monocytic cells. Diabetes 52:1256-1264.
48. Halili MA, et al. (2010) Differential effects of selective HDAC inhibitors on macrophage inflammatory responses to the Toll-like receptor 4 agonist LPS. J. Leukoc. Biol. 87:1103-1114.
49. Leoni F, et al. (2005) The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol. Med. 11:1-15.
50. Choi K, Kim YB. (2010) Molecular mechanism of insulin resistance in obesity and type 2 diabetes. Korean J. Intern. Med. 25:119-129.
51. Greenbaum CJ. (2002) Insulin resistance in type 1 diabetes. Diabetes Metab. Res. Rev. 18:192-200.
52. Scheen AJ. (2005) Diabetes mellitus in the elderly: insulin resistance and/or impaired insulin secretion? Diabetes Metab. 31:5S27-5S34.
53. Mercado MM, McLenithan JC, Silver KD, Shuldiner AR. (2002) Genetics of insulin resistance. Curr. Diab. Rep. 2:83-95.
54. Takigawa-Imamura H, et al. (2003) Stimulation of glucose uptake in muscle cells by prolonged treatment with scriptide, a histone deacetylase inhibitor. Biosci. Biotechnol. Biochem. 67:1499-1506.
55. Kaiser C, James SR. (2004) Acetylation of insulin receptor substrate-1 is permissive for tyrosine phosphorylation. BMC Biol 2:23.
56. Ren JM, et al. (1995) Overexpression of Glut4 protein in muscle increases basal and insulinstimulated whole body glucose disposal in conscious mice. J. Clin. Invest. 95:429-432.
57. Leturque A, Loizeau M, Vaulont S, Salminen M, Girard J. (1996) Improvement of insulin action in diabetic transgenic mice selectively overexpress-ing GLUT4 in skeletal muscle. Diabetes 45:23-27.
58. Thai MV, Guruswamy S, Cao KT, Pessin JE, Olson AL. (1998) Myocyte enhancer factor 2 (MEF2)-binding site is required for GLUT4 gene expression in transgenic mice: regulation of MEF2 DNA binding activity in insulin-deficient diabetes. J. Biol. Chem. 273:14285-14292.
59. McGee SL, et al. (2008) AMP-activated protein ki-nase regulates GLUT4 transcription by phospho-rylating histone deacetylase 5. Diabetes 57:860-867.
60. Sparling DP, Griesel BA, Weems J, Olson AL. (2008) GLUT4 enhancer factor (GEF) interacts with MEF2A and HDAC5 to regulate the GLUT4 promoter in adipocytes. J. Biol. Chem. 283:7429-7437.
61. McKinsey TA, Zhang CL, Olson EN. (2001) Control of muscle development by dueling HATs and HDACs. Curr. Opin. Genet. Dev. 11:497-504.
62. McKinsey TA, Zhang CL, Olson EN. (2000) Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to hi-stone deacetylase 5. Proc. Natl. Acad. Sci. U. S. A. 97:14400-14405.
63. McGee SL, Hargreaves M. (2004) Exercise and myocyte enhancer factor 2 regulation in human skeletal muscle. Diabetes 53:1208-1214.
64. Michael LF, et al. (2001) Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1. Proc. Natl. Acad. Sci. U. S. A. 98:3820-3825.
65. Crunkhorn S, et al. (2007) Peroxisome proliferator activator receptor gamma coactivator-1 expression is reduced in obesity: potential pathogenic role of saturated fatty acids and p38 mitogen-ac-tivated protein kinase activation. J. Biol. Chem. 282:15439-15450.
66. Bonen A. (2009) PGC-1alpha-induced improvements in skeletal muscle metabolism and insulin sensitivity. Appl. Physiol. Nutr. Metab. 34:307-314.
67. McGee SL, Hargreaves M. (2010) Histone modifications and skeletal muscle metabolic gene expression. Clin. Exp. Pharmacol. Physiol. 37:392-396.
68. Verrotti A, D'Egidio C, Mohn A, Coppola G, Chiarelli F. (2010) Weight gain following treatment with valproic acid: pathogenetic mechanisms and clinical implications. Obes. Rev. 12:e32-e43.
69. Verrotti A, et al. (2002) Insulin resistance in epileptic girls who gain weight after therapy with valproic acid. J. Child Neurol. 17:265-268.
70. Pylvanen V, et al. (2002) Serum insulin and leptin levels in valproate-associated obesity. Epilepsia 43:514-517.
71. Pylvanen V, Pakarinen A, Knip M, Isojarvi J. (2006) Characterization of insulin secretion in valproate-treated patients with epilepsy. Epilepsia 47:1460-1464.
72. Lagger G, et al. (2002) Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression. EMBO J. 21:2672-2681.
73. Bhaskara S, et al. (2008) Deletion of histone deacety-lase 3 reveals critical roles in S phase progression and DNA damage control. Mol. Cell 30:61-72.
74. Majdzadeh N, et al. (2008) HDAC4 inhibits cell-cycle progression and protects neurons from cell death. Dev. Neurobiol. 68:1076-1092.
75. Collombat P, Hecksher-Sorensen J, Serup P, Man-souri A. (2006) Specifying pancreatic endocrine cell fates. Mech. Dev. 123:501-512.
76. Chakrabarti SK, Mirmira RG. (2003) Transcription factors direct the development and function of pancreatic beta cells. Trends Endocrinol. Metab. 14:78-84.
77. Ohlsson H, Karlsson K, Edlund T. (1993) IPF1, a homeodomain-containing transactivator of the insulin gene. EMBO J. 12:4251-4259.
78. Jonsson J, Carlsson L, Edlund T, Edlund H. (1994) Insulin-promoter-factor 1 is required for pancreas development in mice. Nature 371:606-609.
79. Offield MF, et al. (1996) PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development 122:983-995.
80. Gradwohl G, Dierich A, LeMeur M, Guillemot F. (2000) Neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Proc. Natl. Acad. Sci. U. S. A. 97:1607-1611.
81. Gu G, Dubauskaite J, Melton DA. (2002) Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 129:2447-2457.
82. Haumaitre C, Lenoir O, Scharfmann R. (2008) Hi-stone deacetylase inhibitors modify pancreatic cell fate determination and amplify endocrine progenitors. Mol. Cell. Biol. 28:6373-6383.
83. Sosa-Pineda B, Chowdhury K, Torres M, Oliver G, Gruss P. (1997) The Pax4 gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreas. Nature 386:399-402.
84. Iguchi H, et al. (2007) SOX6 suppresses cyclin D1 promoter activity by interacting with beta-catenin and histone deacetylase 1, and its down-regulation induces pancreatic beta-cell proliferation. J. Biol. Chem. 282:19052-19061.
85. Noel ES, et al. (2008) Organ-specific requirements for Hdac1 in liver and pancreas formation. Dev. Biol. 322:237-250.
86. Farooq M, et al. (2008) Histone deacetylase 3 (hdac3) is specifically required for liver development in zebrafish. Dev. Biol. 317:336-353.
87. Bradner JE, et al. (2010) Chemical genetic strategy identifies histone deacetylase 1 (HDAC1) and HDAC2 as therapeutic targets in sickle cell disease. Proc. Natl. Acad. Sci. U. S. A. 107:12617-22.
88. Matalon S, et al. (2010) The histone deacetylase inhibitor ITF2357 decreases surface CXCR4 and CCR5 expression on CD4(+) T-cells and monocytes and is superior to valproic acid for latent HIV-1 expression in vitro. J. Acquir. Immune Defic. Syndr. 54:1-9.
89. Goicoa S, Alvarez S, Ricordi C, Inverardi L, Dominguez-Bendala J. (2006) Sodium butyrate activates genes of early pancreatic development in embryonic stem cells. Cloning Stem Cells 8:140-149.
90. Lee JH, Hart SR, Skalnik DG. (2004) Histone deacetylase activity is required for embryonic stem cell differentiation. Genesis 38:32-38.
91. Li L, et al. (2008) Combination of GLP-1 and sodium butyrate promote differentiation of pancreatic progenitor cells into insulin-producing cells. Tissue Cell 40:437-445.
92. Tayaramma T, Ma B, Rohde M, Mayer H. (2006) Chromatin-remodeling factors allow differentiation of bone marrow cells into insulin-producing cells. Stem Cells 24:2858-2867.
93. Jiang J, et al. (2007) Generation of insulin-producing islet-like clusters from human embryonic stem cells. Stem Cells 25:1940-1953.
94. Weiss MA. (2009) Proinsulin and the genetics of diabetes mellitus. J. Biol. Chem. 284:19159-19163.
95. Aramata S, Han SI, Yasuda K, Kataoka K. (2005) Synergistic activation of the insulin gene promoter by the beta-cell enriched transcription factors MafA, Beta2, and Pdx1. Biochim. Biophys. Acta. 1730:41-46.
96. Mosley AL, Corbett JA, Ozcan S. (2004) Glucose regulation of insulin gene expression requires the recruitment of p300 by the beta-cell-specific transcription factor Pdx-1. Mol. Endocrinol. 18:2279-2290.
97. Mosley AL, Ozcan S. (2003) Glucose regulates insulin gene transcription by hyperacetylation of histone h4. J. Biol. Chem. 278:19660-19666.
98. Evans-Molina C, et al. (2007) Glucose regulation of insulin gene transcription and pre-mRNA processing in human islets. Diabetes 56:827-835.
99. Qiu Y, Guo M, Huang S, Stein R. (2002) Insulin gene transcription is mediated by interactions between the p300 coactivator and PDX-1, BETA2, and E47. Mol. Cell. Biol. 22:412-420.
100. Qiu Y, Sharma A, Stein R. (1998) p300 mediates transcriptional stimulation by the basic helix-loop-helix activators of the insulin gene. Mol. Cell. Biol. 18:2957-2964.
101. Mosley AL, Ozcan S. (2004) The pancreatic duodenal homeobox-1 protein (Pdx-1) interacts with histone deacetylases Hdac-1 and Hdac-2 on low levels of glucose. J. Biol. Chem. 279:54241-54247.
102. Qiu Y, Guo M, Huang S, Stein R. (2004) Acetyla-tion of the BETA2 transcription factor by p300-associated factor is important in insulin gene expression. J. Biol. Chem. 279:9796-9802.
103. Han SI, Aramata S, Yasuda K, Kataoka K. (2007) MafA stability in pancreatic beta cells is regulated by glucose and is dependent on its constitutive phosphorylation at multiple sites by glycogen synthase kinase 3. Mol. Cell. Biol. 27:6593-6605.
104. Zhao L, Cissell MA, Henderson E, Colbran R, Stein R. (2000) The RIPE3b1 activator of the insulin gene is composed of a protein(s) of approximately 43 kDa, whose DNA binding activity is inhibited by protein phosphatase treatment. J. Biol. Chem. 275:10532-10537.
105. Guo S, et al. (2009) The stability and transactiva-tion potential of the mammalian MafA transcription factor are regulated by serine 65 phos-phorylation. J. Biol. Chem. 284:759-765.
106. Rocques N, et al. (2007) GSK-3-mediated phos-phorylation enhances Maf-transforming activity. Mol. Cell 28:584-597.
107. Luef GJ, Lechleitner M, Bauer G, Trinka E, Hengster P. (2003) Valproic acid modulates islet cell insulin secretion: a possible mechanism of weight gain in epilepsy patients. Epilepsy Res. 55:53-58.
108. Lundh M, et al. (2010) Lysine deacetylases are produced in pancreatic beta cells and are differentially regulated by proinflammatory cy-tokines. Diabetologia 53:2569-2578.
109. Eizirik DL, Mandrup-Poulsen T. (2001) A choice of death: the signal-transduction of immune-mediated beta-cell apoptosis. Diabetologia 44:2115-2133.
110. Maier B, et al. (2010) The unique hypusine modification of eIF5A promotes islet beta cell inflammation and dysfunction in mice. J. Clin. Invest. 120:2156-2170.
111. Oetjen E, et al. (2007) Inhibition of MafA tran-scriptional activity and human insulin gene transcription by interleukin-1beta and mitogen-activated protein kinase kinase kinase in pancreatic islet beta cells. Diabetologia 50:1678-1687.
112. Atkinson MA, Gianani R. (2009) The pancreas in human type 1 diabetes: providing new answers to age-old questions. Curr. Opin. En-docrinol. Diabetes Obes. 16:279-285.
113. Mandrup-Poulsen T, Bendtzen K, Dinarello CA, Nerup J. (1987) Human tumor necrosis factor potentiates human interleukin 1-mediated rat pancreatic beta-cell cytotoxicity. J. Immunol. 139:4077-4082.
114. Pukel C, Baquerizo H, Rabinovitch A. (1988) Destruction of rat islet cell monolayers by cy-tokines: synergistic interactions of interferon-gamma, tumor necrosis factor, lymphotoxin, and interleukin 1. Diabetes 37:133-136.
115. Cetkovic-Cvrlje M, Eizirik DL. (1994) TNF-alpha and IFN-gamma potentiate the deleterious effects of IL-1 beta on mouse pancreatic islets mainly via generation of nitric oxide. Cy-tokine 6:399-406.
116. Rabinovitch A, et al. (1994) Human pancreatic islet beta-cell destruction by cytokines is independent of nitric oxide production. J. Clin. En-docrinol. Metab. 79:1058-1062.
117. Mandrup-Poulsen T, et al. (1987) Ultrastructural studies of time-course and cellular specificity of interleukin-1 mediated islet cytotoxicity. Acta Pathol. Microbiol. Immunol. Scand. C. 95:55-63.
118. Nielsen K, et al. (1999) Beta-cell maturation leads to in vitro sensitivity to cytotoxins. Diabetes 48:2324-2332.
119. Drage M, et al. (2002) Nondepleting anti-CD4 and soluble interleukin-1 receptor prevent autoimmune destruction of syngeneic islet grafts in diabetic NOD mice. Transplantation 74:611-619.
120. Gysemans C, et al. (2003) Prevention of primary non-function of islet xenografts in autoimmune diabetic NOD mice by anti-inflammatory agents. Diabetologia 46:1115-1123.
121. Sandberg JO, Eizirik DL, Sandler S. (1997) IL-1 receptor antagonist inhibits recurrence of disease after syngeneic pancreatic islet transplantation to spontaneously diabetic non-obese diabetic (NOD) mice. Clin. Exp. Immunol. 108:314-317.
122. Sandberg JO, Eizirik DL, Sandler S, Tracey DE, Andersson A. (1993) Treatment with an inter-leukin-1 receptor antagonist protein prolongs mouse islet allograft survival. Diabetes 42:1845-1851.
123. Tellez N, et al. (2007) Adenoviral overproduction of interleukin-1 receptor antagonist increases beta cell replication and mass in syn-geneically transplanted islets, and improves metabolic outcome. Diabetologia 50:602-611.
124. Amoli MM, Larijani B. (2006) Would blockage of cytokines improve the outcome of pancreatic islet transplantation? Med. Hypotheses 66:816-819.
125. Susick L, Veluthakal R, Suresh MV, Hadden T, Kowluru A. (2008) Regulatory roles for histone deacetylation in IL-1beta-induced nitric oxide release in pancreatic beta-cells. J. Cell. Mol. Med. 12:1571-1583.
126. Susick L, Senanayake T, Veluthakal R, Woster PM, Kowluru A. (2009) A novel histone deacety-lase inhibitor prevents IL-1beta induced metabolic dysfunction in pancreatic beta-cells. J. Cell. Mol. Med. 13:1877-1885.
127. Spinas GA, et al. (1986) Low concentrations of interleukin-1 stimulate and high concentrations inhibit insulin release from isolated rat islets of Langerhans. Acta. Endocrinol. (Copenh.) 113:551-558.
128. Sandler S, Andersson A, Hellerstrom C. (1987) Inhibitory effects of interleukin 1 on insulin secretion, insulin biosynthesis, and oxidative metabolism of isolated rat pancreatic islets. Endocrinology 121:1424-1431.
129. Ohara-Imaizumi M, Cardozo AK, Kikuta T, Eizirik DL, Nagamatsu S. (2004) The cytokine interleukin-1beta reduces the docking and fusion of insulin granules in pancreatic beta-cells, preferentially decreasing the first phase of exo-cytosis. J. Biol. Chem. 279:41271-41274.
130. Ortis F, et al. (2010) Cytokines interleukin-1beta and tumor necrosis factor-alpha regulate different transcriptional and alternative splicing networks in primary beta-cells. Diabetes 59:358-374.
131. Ashburner BP, Westerheide SD, Baldwin AS Jr. (2001) The p65 (RelA) subunit of NF-kappaB interacts with the histone deacetylase (HDAC) core-pressors HDAC1 and HDAC2 to negatively regulate gene expression. Mol. Cell. Biol. 21:7065-7077.
132. Kiernan R, et al. (2003) Post-activation turn-off of NF-kappa B-dependent transcription is regulated by acetylation of p65. J. Biol. Chem. 278:2758-2766.
133. Gysemans CA, et al. (2005) Disruption of the gamma-interferon signaling pathway at the level of signal transducer and activator of tran-scription-1 prevents immune destruction of beta-cells. Diabetes 54:2396-2403.
134. Klampfer L, Huang J, Swaby LA, Augenlicht L. (2004) Requirement of histone deacetylase activity for signaling by STAT1. J. Biol. Chem. 279:30358-30368.
135. Cardozo AK, et al. (2005) Cytokines downregu-late the sarcoendoplasmic reticulum pump Ca2+ ATPase 2b and deplete endoplasmic retic-ulum Ca2+, leading to induction of endoplas-mic reticulum stress in pancreatic beta-cells. Diabetes 54:452-461.
136. Oyadomari S, et al. (2001) Nitric oxide-induced apoptosis in pancreatic beta cells is mediated by the endoplasmic reticulum stress pathway. Proc. Natl. Acad. Sci. U. S. A. 98:10845-10850.
137. Eizirik DL, Cardozo AK, Cnop M. (2008) The role for endoplasmic reticulum stress in diabetes mellitus. Endocr. Rev. 29:42-61.
138. Eizirik DL, Cnop M. (2010) ER stress in pancreatic beta cells: the thin red line between adaptation and failure. Sci Signal 3:pe7.
139. Weber SM, Chambers KT, Bensch KG, Scarim AL, Corbett JA. (2004) PPARgamma ligands induce ER stress in pancreatic beta-cells: ER stress activation results in attenuation of cytokine signaling. Am. J. Physiol. Endocrinol. Metab. 287:E1171-E1177.
140. Mokhtari D, et al. (2009) Increased Hsp70 expression attenuates cytokine-induced cell death in islets of Langerhans from Shb knockout mice. Biochem. Biophys. Res. Commun. 387:553-557.
141. Johnson CA, White DA, Lavender JS, O'Neill LP, Turner BM. (2002) Human class I histone deacetylase complexes show enhanced catalytic activity in the presence of ATP and co-immuno-precipitate with the ATP-dependent chaperone protein Hsp70. J. Biol. Chem. 277:9590-9597.
142. Shi Y, Gerritsma D, Bowes AJ, Capretta A, Werstuck GH. (2007) Induction of GRP78 by val-proic acid is dependent upon histone deacetylase inhibition. Bioorg. Med. Chem. Lett. 17:4491-4494.
143. Laybutt DR, et al. (2007) Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes. Diabetologia 50:752-763.
144. Akerfeldt MC, et al. (2008) Cytokine-induced beta-cell death is independent of endoplasmic reticulum stress signaling. Diabetes 57:3034-3044.
145. Ohoka N, Hattori T, Kitagawa M, Onozaki K, Hayashi H. (2007) Critical and functional regulation of CHOP (C/EBP homologous protein) through the N-terminal portion. J. Biol. Chem. 282:35687-35694.
146. Huang CJ, et al. (2007) High expression rates of human islet amyloid polypeptide induce endo-plasmic reticulum stress mediated beta-cell apo-ptosis, a characteristic of humans with type 2 but not type 1 diabetes. Diabetes 56:2016-2027.
147. Grunnet LG, et al. (2009) Proinflammatory cy-tokines activate the intrinsic apoptotic pathway in beta-cells. Diabetes 58:1807-1815.
148. Chang I, et al. (2004) Role of calcium in pancreatic islet cell death by IFN-gamma/TNF-alpha. J. Immunol. 172:7008-7014.
149. McKenzie MD, et al. (2008) Proapoptotic BH3-only protein Bid is essential for death receptor-induced apoptosis of pancreatic beta-cells. Diabetes 57:1284-1292.
150. Allagnat F, et al. (2011) Mcl-1 downregulation by pro-inflammatory cytokines and palmitate is an early event contributing to β-cell apoptosis. Cell Death Differ. 18:328-337.
151. Gurzov EN, et al. (2010) p53 up-regulated modulator of apoptosis (PUMA) activation contributes to pancreatic beta-cell apoptosis induced by proinflammatory cytokines and endoplasmic reticulum stress. J. Biol. Chem. 285:19910-19920.
152. Gurzov EN, et al. (2009) Signaling by IL-1beta+IFN-gamma and ER stress converge on DP5/Hrk activation: a novel mechanism for pancreatic beta-cell apoptosis. Cell Death Differ. 16:1539-1550.
153. Rabinovitch A, et al. (1999) Transfection of human pancreatic islets with an anti-apoptotic gene (bcl-2) protects beta-cells from cytokine-in-duced destruction. Diabetes 48:1223-1229.
154. Holohan C, Szegezdi E, Ritter T, O'Brien T, Samali A. (2008) Cytokine-induced beta-cell apoptosis is NO-dependent, mitochondria-mediated and inhibited by BCL-XL. J. Cell Mol. Med. 12:591-606.
155. Chen S, Dai Y, Pei XY, Grant S. (2009) Bim up-regulation by histone deacetylase inhibitors mediates interactions with the Bcl-2 antagonist ABT-737: evidence for distinct roles for Bcl-2, Bcl-xL, and Mcl-1. Mol. Cell. Biol. 29:6149-6169.
156. Ruefli AA, et al. (2001) The histone deacetylase inhibitor and chemotherapeutic agent suberoy-lanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of Bid and production of reactive oxygen species. Proc. Natl. Acad. Sci. U. S. A. 98:10833-10838.
157. Sutheesophon K, et al. (2006) Histone deacety-lase inhibitor depsipeptide (FK228) induces apoptosis in leukemic cells by facilitating mito-chondrial translocation of Bax, which is enhanced by the proteasome inhibitor bortezomib. Acta. Haematol. 115:78-90.
158. Cao XX, Mohuiddin I, Ece F, McConkey DJ, Smythe WR. (2001) Histone deacetylase inhibitor downregulation of bcl-xl gene expression leads to apoptotic cell death in mesothe-lioma. Am. J. Respir. Cell Mol. Biol. 25:562-568.