Genetic and molecular basis of QTL of diabetes in mouse: Genes and polymorphisms

Current Genomics

Volumn 9, Issue 5, 2008, Pages 324-337

  Gao, Peng ^a   Jiao, Yan ^a   Xiong, Qing ^a   Wang, Cong Yi ^b   Gerling, Ivan ^a   Gu, Weikuan ^a  

^a UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^b MEDICAL COLLEGE OF GEORGIA   (United States)

Author keywords

Candidate gene; Insulin dependent diabetes mellitus (IDDM); Mouse; Polymorphism; Quantitative trait loci; Type 1 diabetes

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); ALKALINE PHOSPHATASE; AMYLASE; AROMATIC HYDROCARBON RECEPTOR; BETA 2 MICROGLOBULIN; CASPASE RECRUITMENT DOMAIN PROTEIN 15; CD4 ANTIGEN; CD69 ANTIGEN; CELL NUCLEUS RECEPTOR; COLONY STIMULATING FACTOR 1; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; EPIDERMAL GROWTH FACTOR RECEPTOR 4; FC RECEPTOR; GALANIN LIKE PEPTIDE; GLUCAGON LIKE PEPTIDE 1; HISTONE DEACETYLASE 1; HOMEODOMAIN PROTEIN; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 21; INTERLEUKIN 21 RECEPTOR; PROTEIN CDC42; PROTEIN KINASE LCK; PROTEIN KINASE ZAP 70; PROTEIN TYROSINE PHOSPHATASE; SEMAPHORIN 3A; SYNAPTOSOMAL ASSOCIATED PROTEIN 25; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 9; TRANSCRIPTION FACTOR E2F2;

CHROMOSOME 1; CHROMOSOME 11; CHROMOSOME 13; CHROMOSOME 14; CHROMOSOME 17; CHROMOSOME 2; CHROMOSOME 3; CHROMOSOME 4; CHROMOSOME 5; CHROMOSOME 6; CHROMOSOME 7; CHROMOSOME 8; CHROMOSOME 9; GENE IDENTIFICATION; GENE SEQUENCE; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC LINKAGE; GENETIC POLYMORPHISM; GENETIC VARIABILITY; INHERITANCE; INSULIN DEPENDENT DIABETES MELLITUS; MEDICAL RESEARCH; MEDLINE; MOLECULAR MECHANICS; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; QUANTITATIVE TRAIT LOCUS; QUANTITATIVE TRAIT LOCUS MAPPING; REVIEW;

EID: 49749144474     PISSN: 13892029     EISSN: None     Source Type: Journal    
DOI: 10.2174/138920208785133253     Document Type: Review

References (181)

1. Salojin, K., Zhang, J., Cameron, M., Gill, B., Arreaza, G., Ochi, A., Delovitch, T.L. Impaired plasma membrane targeting of Grb2-murine son of sevenless (mSOS) complex and differential activation of the Fyn-T cell receptor (TCR)-zeta-Cb1 pathway mediate T cell hyporesponsiveness in autoimmune nonobese diabetic mice. J. Exp. Med. 1997, 186: 887-97.
2. Ueda, H., Howson, J.M., Esposito, L., Heward, J., Snook, H., Chamberlain, G., Rainbow, D.B., Hunter, K.M., Smith, A.N., Di, Genova, G., Herr, M.H., Dahlman, I., Payne, F., Smyth, D., Lowe, C., Twells, R.C., Howlett, S., Healy, B., Nutland, S., Rance, H.E., Everett, V., Smink, L.J., Lam, A.C., Cordell, H.J., Walker, N.M., Bordin, C., Hulme, J., Motzo, C., Cucca, F., Hess, J.F., Metzker, M.L., Rogers, J., Gregory, S., Allahabadia, A., Nithiyananthan, R., Tuomilehto-Wolf, E., Tuomilehto, J., Bingley, P., Gillespie, K.M., Undlien, D.E., Rønningen, K.S., Guja, C., Ionescu-Tirgoviste, C., Savage, D.A., Maxwell, A.P., Carson, D.J., Patterson, C.C., Franklyn, J.A., Clayton, D.G., Peterson, L.B., Wicker, L.S., Todd, J.A., Gough, S.C. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 2003, 423: 506-11.
3. Wicker, L.S., Chamberlain, G., Hunter, K., Rainbow, D., Howlett, S., Tiffen P., Clark, J., Gonzalez-Munoz, A., Cumiskey, AM., Rosa, R.L., Howson, J.M., Smink, L.J., Kingsnorth, A., Lyons, P.A., Gregory, S., Rogers, J., Todd, J.A., Peterson, L.B. Fine mapping, gene content, comparative sequencing, and expression analyses support Ctla4 and Nramp1 as candidates for Idd.5.1 and Idd5.2 in the nonobese diabetic mouse. J. Immunol. 2004, 173: 164-73.
4. Chen, Z., Stockton, J., Mathis, D., Benoist, C. Modeling CTLA4-linked autoimmunity with RNA interference in mice. Proc. Natl. Acad. Sci. USA 2006, 103: 16400-5.
5. Lundholm, M., Motta, V., Löfgren-Burström, A., Duarte, N., Bergman, M.L., Mayans, S., Holmberg D. Defective induction of CTLA-4 in the NOD mouse is controlled by the NOD allele of Idd3/IL-2 and a locus (Ctex) telomeric on chromosome 1. Diabetes 2006, 55: 538-44.
6. Ihara, K., Ahmed, S., Nakao, F., Kinukawa, N., Kuromaru, R., Matsuura, N., Iwata, I., Nagafuchi, S., Kohno, H., Miyako, K., Hara, T. Association studies of CTLA-4., CD28., and Icos gene polymorphisms with T1D in the Japanese population. Immunogenetics 2001, 53: 447-54.
7. Bour-Jordan, H., Salomon, B.L., Thompson, H.L., Szot, G.L., Bernhard, M.R., Bluestone, J.A. Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells. J. Clin. Invest. 2004, 114: 979-87.
8. Xuguang, Tai., Francois, Van, Laethem., Arlene, H. Sharpe., and Alfred Singer. Induction of autoimmune disease in CTLA-4-/- mice depends on a specific CD28 motif that is required for in vivo costimulation. Proc. Natl. Acad. Sci. USA 2007, 104: 13756-61.
9. Colucci, F., Bergman, M.L., Penha-Gonçalves, C., Cilio, C.M., Holmberg, D. Apoptosis resistance of nonobese diabetic peripheral lymphocytes linked to the Idd5 diabetes susceptibility region. Proc. Natl. Acad. Sci. USA 1997, 94: 8670-4.
10. Herman, A.E., Freeman, G.J., Mathis, D., Benoist, C. CD4+CD25+ T regulatory cells dependent on icos promote regulation of effector cells in the prediabetic lesion. J. Exp. Med. 2004, 199: 1479-89.
11. Greve, B., Vijayakrishnan, L., Kubal, A., Sobel, RA., Peterson, LB., Wicker, L.S., Kuchroo, V.K. The diabetes susceptibility locus Idd5.1 on mouse chromosome 1 regulates icos expression and modulates murine experimental autoimmune encephalomyelitis. J. Immunol. 2004, 173: 157-63.
12. Takahashi, K., Satoh, J., Kojima, Y., Negoro, K., Hirai, M., Hinokio, Y., Kinouchi, Y., Suzuki, S., Matsuura, N., Shimosegawa, T., Oka, Y. Promoter polymorphism of sclc11a1(formerly NRAMP1) confers susceptibility to autoimmune T1D mellitus in Japanese. Tissue Antigens 2004, 63: 231-6.
13. Kissler, S., Stern, P., Takahashi, K., Hunter, K., Peterson, LB., Wicker, L.S. In vivo RNA interference demonstrates a role for Nramp1 in modifying susceptibility to T1D. Nat. Genet. 2006, 38: 479-83.
14. Morrison, V.A., Onengut-Gumuscu, S., Concannon, P. A functional variant of IRS1 is associated with T1D in families from the US and UK. Mol. Genet. Metab. 2004, 81: 291-4.
15. Eftychi, C., Howson, J.M., Barratt, B.J., Vella A., Payne, F., Smyth, D.J., Twells, R.C., Walker, N.M., Rance, H.E., Tuomilehto-Wolf, E., Tuomilehto, J., Undlien, D.E., Rønningen, K.S., Guja, C., Ionescu-Tîrgoviste, C., Savage, D.A., Todd, J.A. Analysis of the type 2 diabetes-associated single nucleotide polymorphisms in the genes IRS1, KCNJ11, and PPARG2 in T1D. Diabetes 2004, 53: 870-3.
16. Irie, J., Reck, B., Wu, Y., Wicker, L.S., Howlett, S., Rainbow, D., Feingold, E., Ridgway, W.M. Genome-Wide Microarray Expression Analysis of CD4+ T Cells from Nonobese Diabetic Congenic Mice Identifies Cd55 (Daf1) and Acadl as Candidate Genes for T1D. J. Immunol. 2008, 180: 1071-9.
17. Liadis, N., Salmena, L., Kwan, E., Tajmir, P., Schroer, SA., Radziszewska, A., Li, X., Sheu, L., Eweida, M., Xu, S., Gaisano, H.Y., Hakem, R., Woo, M. Distinct in vivo roles of caspase-8 in beta-cells in physiological and diabetes models. Diabetes 2007, 56: 2302-11.
18. Huotari, M.A., Miettinen, P.J., Palgi, J., Koivisto, T., Ustinov, J., Harari, D., Yarden, Y., Otonkoski, T. ErbB signaling regulates lineage determination of developing pancreatic islet cells in embryonic organ culture. Endocrinology 2002, 143: 4437-46.
19. Thomas, M.K., Rastalsky, N., Lee, J.H., Habener, J.F. Hedgehog signaling regulation of insulin production by pancreatic beta-cells. Diabetes 2000, 49: 2039-47.
20. Ball, A.J., Abrahamsson, A.E., Tyrberg, B., Itkin-Ansari, P., Levine, F. HES6 reverses nuclear reprogramming of insulin-producing cells following cell fusion. Biochem. Biophys. Res. Commun. 2007, 355: 331-7.
21. Serreze, D.V., Leiter, E.H., Christianson, G.J., Greiner, D., Roopenian, D.C. Major histocompatibility complex class I-deficient NOD-B2mnull mice are diabetes and insulitis resistant. Diabetes 1994, 43: 505-9.
22. Serreze, D.V., Bridgett, M., Chapman, HD., Chen, E., Richard, S.D., Leiter, E.H. Subcongenic analysis of the Idd13 locus in NOD/Lt mice: evidence for several susceptibility genes including a possible diabetogenic role for beta 2-microglobulin. J. Immunol. 1998, 160: 1472-8.
23. Zraika, S., Dunlop, M.E., Proietto, J., Andrikopoulos, S. Elevated, SNAP-25 is associated with fatty acid-induced impairment of mouse islet function. Biochem. Biophys. Res. Commun. 2004, 317: 472-7.
24. Nagamatsu, S., Nakamichi, Y., Yamamura, C., Matsushima, S., Watanabe, T., Ozawa, S., Furukawa, H., Ishida, H. Decreased expression of t-SNARE, syntaxin 1, and SNAP-25 in pancreatic beta-cells is involved in impaired insulin secretion from diabetic GK rat islets: restoration of decreased t-SNARE proteins improves impaired insulin secretion. Diabetes 1999, 48: 2367-73.
25. Kaizer, E.C., Glaser, C.L., Chaussabel, D., Banchereau, J., Pascual, V., White PC. Gene expression in peripheral blood mononuclear cells from children with diabetes. J. Clin. Endocrinol. Metab. 2007, 92: 3705-11.
26. Kim, H.S., Han, M.S., Chung, K.W., Kim, S., Kim, E., Kim, MJ., Jang, E., Lee, H.A., Youn, J., Akira, S., Lee, M.S. Toll-like receptor 2 senses beta-cell death and contributes to the initiation of autoimmune diabetes. Immunity 2007, 27: 183-5.
27. Park, Y., Park S., Yoo, E., Kim, D., Shin, H. Association of the polymorphism for Toll-like receptor 2 with T1D susceptibility. Ann. N. Y. Acad. Sci. 2004, 1037: 170-4.
28. Yamaji, K., Ikegami, H., Fujisawa, T., Noso, S., Nojima, K., Babaya, N., Itoi-Babaya, M., Makino, S., Sakamoto, T., Ogihara, T. Evidence for Gd101 but not Fcgr1 as candidate for T1D locus, Idd10. Biochem. Biophys. Res. Commun. 2005, 331: 536-42.
29. Héron, L., Virsolvy, A., Apiou, F., Le, Cam, A., Bataille, D. Isolation., characterization., and chromosomal localization of the human ENSA gene that encodes alpha-endosulfine, a regulator of beta-cell K(ATP) channels. Diabetes 1999, 48: 1873-6.
30. Mirasierra, M., Vallejo, M. The homeoprotein Alx3 expressed in pancreatic beta-cells regulates insulin gene transcription by interacting with the basic helix-loop-helix protein E47. Mol. Endocrinol. 2006, 20: 2876-89.
31. Wandstrat, A.E., Nguyen, C., Limaye, N., Chan, A.Y., Subramanian, S., Tian, X.H., Yim, Y.S., Pertsemlidis, A., Garner, H.R Jr., Morel, L., Wakeland, E.K. Association of extensive polymorphisms, in the SLAM/CD2 gene cluster with murine lupus. Immunity 2004, 21: 769-80.
32. Onengut-Gumuscu, S., Buckner, J.H., Concannon, P. A haplotype-based analysis of the PTPN22 locus in T1D. Diabetes 2006, 55: 2883-9.
33. Hermann, R., Lipponen, K., Kiviniemi, M., Kakko, T., Veijola, R., Simell, O., Knip, M., Ilonen, J. Lymphoid tyrosine phosphatase (LYP/ PTPN22) Arg620Trp variant regulates insulin autoimmunity and progression to T1D. Diabetologia 2006, 49: 1198-208.
34. Bekris, L.M., Shephard, C., Peterson, M., Hoehna, J., Van, Yserloo, B., Rutledge, E., Farin, F., Kavanagh, T.J., Lernmark, A. Glutathione-s-transferase M1 and T1 polymorphisms and associations with T1D age-at-onset Autoimmunity 2005, 38: 567-75.
35. Hegazy, D., O'Reill,y D., Yang, B., Hodgkinson, A., Millward, B., Demaine, A. NFkappaB polymorphisms and susceptibility to T1D. Genes Immun. 2001, 2: 304-8.
36. Katarina, K., Daniela, P., Peter, N., Marianna, R., Pavlina, C., Stepanka, P., Jan, L., Ludmila, T., Michal, A., Marie C. HLA, NFKB1 and NFKBIA gene polymorphism profile in autoimmune diabetes mellitus patients. Exp. Clin. Endocrinol. Diabetes 2007, 115: 124-9.
37. Gylvin, T., Bergholdt, R., Nerup, J., Pociot, F. Characterization of a nuclear-factor-kappa B (NFkappaB) genetic marker in T1D (T1D) families. Genes Immun. 2002, 3: 430-2.
38. Hodge, S.E., Anderson, C.E., Neiswanger, K., Rubin, R., Sparkes, R.S., Sparkes, M.C., Crist, M., Spence, M.A., Terasaki, P.I., Rimoin, D.L. Association studies between Type 1 (insulin-dependent) diabetes and 27 genetic markers: lack of association between T1D and Kidd blood group. Diabetologia 1983, 25: 343-7.
39. Maier, L.M., Smyth, D.J., Vella, A., Payne, F., Cooper, J.D., Pask, R., Lowe, C., Hulme, J., Smink, L.J., Fraser, H., Moule, C., Hunter, K.M., Chamberlain, G., Walker, N., Nutland, S., Undlien, D.E., Rønningen, K.S., Guja, C., Ionescu-Tirgoviste, C., Savage, D.A., Strachan, D.P., Peterson, L.B., Todd, J.A., Wicker, L.S., Twells, R.C. Construction and analysis of tag single nucleotide polymorphism maps for six human-mouse orthologous candidate genes in T1D. BMC Genet. 2005, 6: 9.
40. Ikegami, H., Fujisawa, T., Sakamoto, T., Makino, S., Ogihara, T. Idd1 and Idd3 are necessary but not sufficient for development of T1D in NOD mouse. Diabetes Res. Clin. Pract. 2004, 66: S85-90.
41. Ikegami, H., Fujisawa, T., Makino, S., Ogihara, T. Congenic mapping and candidate sequencing of susceptibility genes for T1D in the NOD mouse. Ann. N. Y. Acad. Sci. 2003, 1005: 196-204.
42. Asano, K., Ikegami, H., Fujisawa, T., Nishino, M., Nojima, K., Kawabata, Y., Noso, S., Hiromine, Y., Fukai, A., Ogihara, T. Molecular scanning of interleukin-21 gene and genetic susceptibility to T1D. Hum. Immunol. 2007, 68: 384-91.
43. Asano, K., Ikegami, H., Fujisawa, T., Kawabata, Y., Noso S., Hiromine, Y., Ogihara, T. The gene for human IL-21 and genetic susceptibility to T1D in the Japanese. Ann. N. Y. Acad. Sci. 2006, 1079: 47-50.
44. Fowlkes, JL., Bunn, R.C., Liu, L., Wahl, E.C., Coleman, H.N., Cockrell, G.E., Perrien, D.S., Lumpkin, C.K. Jr., Thrailkill, K.M. Runt-related transcription factor 2 (RUNX2) and RUNX2-related osteogcnic genes are downregulated throughout osteogenesis in T1D mellitus. Endocrinology 2008, 149: 1697-1704.
45. Makita, Y., Moczulski, D.K., Bochenski, J., Smiles, A.M., Warram, J.H., Krolewski, A.S. Methylenetetrahydrofolate reductase gene polymorphism and susceptibility to diabetic nephropathy in T1D. Am. J. Kidney Dis. 2003, 41: 1189-94.
46. J. Smyth, D. Savage, A. Maxwell. MTHFR gene polymorphism and diabetic nephropathy in T1D. Lancet 1999, 353: 1156-7.
47. Neugebauer, S., Baba, T., Watanabe, T. Methylenetetrahydrofolate reductase gene polymorphism as a risk factor for diabetic nephropathy in NIDDM patients. Lancet 1998, 352: 454.
48. Suvannavejh, G.C., Lee, H.O., Padilla, J., Dal, Canto, M.C., Barrett, T.A., Miller, S.D. Divergent roles for p55 and p75 tumor necrosis factor receptors in the pathogenesis of MOG(35-55)-induced experimental autoimmune encephalomyelitis. Cell. Immunol. 2000, 205: 24-33.
49. Trendelenburg, M., Manderson, A.P., Fossati-Jimack, L., Walport, M.J., Botto, M. Monocytosis and accelerated activation of lymphocytes in C1q-deficient autoimmune-prone mice. Immunology 2004, 113: 80-8.
50. Miura-Shimura, Y., Nakamura, K., Ohtsuji, M., Tomita, H., Jiang, Y., Abe, M., Zhang, D., Hamano, Y., Tsuda, H., Hashimoto, H., Nishimura, H., Taki, S., Shirai, T., Hirose, S. C1q regulatory region polymorphism down-regulating murine c1q protein levels with linkage to lupus nephritis. J. Immunol. 2002, 169: 1334-9.
51. Chen, Z., Koralov, S.B., Kelsoe, G. Complement C4 inhibits systemic autoimmunity through a mechanism independent of complement receptors CR1 and CR2. J. Exp. Med. 2000, 192: 1339-52.
52. Nervi, S., Nicodeme, S., Gartioux, C., Atlan, C., Lathrop, M., Reviron, D., Naquet P,, Matsuda, F., Imbert, J., Vialettes, B. No association between lck gene polymorphisms and protein level in T1D. Diabetes 2002, 51: 3326-30.
53. Hulme, J.S., Barratt, B.J., Twells, R.C., Cooper, J.D., Lowe, C.E., Howson, J.M., Lam, A.C., Smink, L.J., Savage, D.A., Undlien, D.E., Guja, C., Ionescu-Tiirgoviste, C., Tuomilehto-Wolf, E., Tuomilehto, J., Todd, J.A. Association analysis of the lymphocyte-specific protein tyrosine kinase (LCK) gene in T1D. Diabetes 2004, 53: 2479-82.
54. Smyth, D.J., Howson, J.M., Payne, F,, Maier, L.M., Bailey, R., Holland, K., Lowe, C.E., Cooper, J.D., Hulme, J.S., Vella, A., Dahlman, I., Lam, A.C., Nutland, S., Walker, N.M., Twells, R.C., Todd, J.A. Analysis of polymorphisms in 16 genes in T1D that have been associated with other immune-mediated diseases. BMC Med. Genet. 2006, 7: 20.
55. Fan, H., Patel, V.A., Longacre, A., Levine, J.S. Abnormal regulation of the cytoskeletal regulator Rho typifies macrophages of the major murine models of spontaneous autoimmunity. J. Leukoc. Biol. 2006, 79: 155-65.
56. Brodnicki, T.C., McClive, P., Couper, S., Morahan, G. Localization of Idd11 using NOD congenic mouse strains: elimination of Slc9a1 as a candidate gene. Immunogenetics 2000, 51: 37-41.
57. Li, F.X., Zhu, J.W., Tessem, J.S., Beilke, J., Varella-Garcia, M., Jensen, J., Hogan, C.J., DeGregori, J. The development of diabetes in E2f1/E2f2 mutant mice reveals important roles for bone marrow-derived cells in preventing islet cell loss. Proc. Natl. Acad. Sci. USA 2003, 100: 12935-40.
58. Cannons, J.L., Chamberlain, G., Howson, J., Smink, I.J., Todd, J.A., Peterson, L.B., Wicker, L.S., Watts, T.H. Genetic and functional association of the immune signaling molecule 4-IBB (CD137/TNFRSF9) with T1D. J.Autoimmun. 2005, 25: 13-20.
59. Yamamoto, M., Suzuki, K., Okuno, T., Ogata, T., Takegahara, N., Takamatsu, H., Mizui, M., Taniguchi, M., Chédotal, A., Suto, F., Fujisawa, H., Kumanogoh, A., Kikutani, H. Plexin-A4 negatively regulates T lymphocyte responses. Int. Immunol. 2008, 20: 413-20.
60. Ilonen, J., Surcel, H.M., Käär, M.L. Abnormalities within CD4 and CD8 T lymphocytes subsets in type 1 (insulin-dependent) diabetes. Clin. Exp. Immunol. 1991, 85: 278-81.
61. Green, E.A., Choi, Y., Flavell, R.A. Pancreatic Lymph Node-Derived CD4+CD25+ Treg Cells: Highly Potent Regulators of Diabetes that Require TRANCE-RANK Signals. Immunity 2002, 16: 183-91.
62. Salomon, B., Lenschow, D.J., Rhee, L., Ashourian, N., Singh, B., Sharpe, A., Bluestone, J.A. B7/CD28 Costimulation Is Essential for the Homeostasis of the CD4+CD25+ Immunoregulatory T Cells that Control Autoimmune Diabetes. Immunity 2000, 12: 431-40.
63. Green, E.A., Gorelik, L., McGregor, C.M., Tran, E.H., Flavell, R.A. CD4+CD25+ T regulatory cells control anti-islet CD8+ T cells through TGF-beta-TGF-beta receptor interactions in TiD. Proc. Natl. Acad. Sci. USA 2003, 100: 10878-83.
64. Sancho, D., Gómez, M., Viedma, F., Esplugues, E., Gordón-Alonso, M., García-López, M.A., de, la, Fuente, H., Martínez-A, C., Lauzurica, P., Sánchez-Madrid, F. CD69 downregulates autoimmune reactivity through active transforming growth factor-beta production in collagen-induced arthritis. J. Clin. Invest. 2003, 112: 872-82.
65. Giordano, C., De Maria, R., Todaro, M., Stassi, G., Mattina, A., Richiusa, P., Galluzzo, G., Pantó F., Galluzzo, A. Study of T-cell activation in type I diabetic patients and pre-type I diabetic subjects by cytometric analysis: antigen expression defect in vitro. J. Clin. Immunol. 1993, 13: 68-78.
66. Geluk, A., van Meijgaarden, K.E., Roep, B.O., Ottenhoff, T.H. Altered peptide ligands of islet autoantigen Imogen 38 inhibit antigen specific T cell reactivity in human type-1 diabetes. J. Autoimmun. 1998, 11: 353-61.
67. Estella, E., McKenzie, M.D., Catterall, T., Sutton, V.R., Bird, P.I., Trapani, J.A., Kay, T.W., Thomas, H.E. Granzyme B-mediated death of pancreatic beta-cells requires the proapoptotic BH3-only molecule bid. Diabetes 2006, 55: 2212-9.
68. Grimm, C.H., Rogner, U.C., Avner, P. Lrmp and Bcat1 are candidates for the type 1 diabetes susceptibility locus Idd6. Autoimmunity 2003, 36: 241-6.
69. Duarte, N., Lundholm, M., Holmberg, D. The Idd6.2 diabetes susceptibility region controls defective expression of the Lrmp gene in nonobese diabetic (NOD) mice. Immunogenetics 2007, 59: 407-16.
70. Rampersaud, E., Damcott, C.M., Fu, M., Shen, H., McArdle, P., Shi, X., Shelton, J., Yin, J., Chang, Y.P., Ott, S.H., Zhang, L., Zhao, Y., Mitchell, B.D., O'Connell, J., Shuldiner, A.R. Identification of candidate genes for type 2 diabetes from a genome-wide association scan in the Old Order Amish: evidence for replication from diabetes-related quantitative traits and from independent populations. Diabetes 2007, 56: 3053-62.
71. Siffert, W. G protein beta 3 subunit 825T allele, hypertension, obesity, and diabetic nephropathy. Nephrol. Dial. Transplant. 2000, 15: 1298-306.
72. Hung, M.S., Avner, P., Rogner, U.C. Identification of the transcription factor ARNTL2 as a candidate gene for the T1D locus Idd6. Hum. Mol. Genet. 2006, 15: 2732-42.
73. Sharp, C.D., Huang, M., Glawe, J., Patrick, D.R., Pardue, S., Barlow, S.C., Kevil, C.G. Stromal cell-derived factor-1/CXCL12 stimulates chemorepulsion of NOD/LtJ T-cell adhesion to islet microvascular endothelium. Diabetes 2008, 57: 102-12.
74. Feng, D., Bursell, S.E., Clermont, A.C., Lipinska, I., Aiello, L.P., Laffel, L., King, G.L., Tofler, G.H. von Willebrand factor and retinal circulation in early-stage retinopathy of T1D. Diabetes Care 2000, 23: 1694-8.
75. Ouyang, Q., Standifer, N.E., Qin, H., Gottlieb, P., Verchere, C.B., Nepom, G.T., Tan, R., Panagiotopoulos C. Recognition of HLA class I-restricted beta-cell epitopes in T1D. Diabetes 2006, 55: 3068-74.
76. Beisswenger, P.J., Howell, S.K., Smith, K., Szwergold, B.S. Glyceraldehyde-3-phosphate dehydrogenase activity as an independent modifier of methylglyoxal levels in diabetes. Biochim. Biophys. Acta 2003, 1637: 98-106.
77. Oh, E., Heise, C.J., English, J.M., Cobb, M.H., Thurmond, D.C. WNK1 is a regulator of Munc18c-syntaxin 4 complex formation in soluble NSF attachment protein receptor (SNARE)-mediated vesicle exocytosis. J. Biol. Chem. 2007, 282: 32613-22.
78. Brown, S.D., Twells, R.C., Hey, P.J., Cox, R.D., Levy, E.R., Soderman, A.R., Metzker, M.L., Caskey, C.T., Todd, J.A., Hess, J.F. Isolation and characterization of LRP6, a member of the low density lipoprotein receptor gene family. Biochem. Biophys. Res. Commun. 1998, 248: 879-88.
79. Gumprecht, J., Zychma, MJ., Grzeszczak, W., Zukowska-Szczechowska, E., End-Stage Renal Disease Study Group. Transmission of G-protein beta3 subunit C825T alleles to offspring affected with end-Stage renal disease. Am. J. Nephrol. 2001, 21: 368-72.
80. Hyöty, H., Pandey, J.P., Lehtinen, M., Kulomaa, P., Leinikki, P. Immunoglobulin allotypes and virus antibodies in Finnish type 1 diabetic patients. Exp. Clin. Immunogenet. 1988, 5: 52-9.
81. Saito, T., Tojo, K., Kuriyama, G., Murakawa, Y., Fujimoto, K., Taniguchi, K., Tanii, K., Katakami, H., Hashimoto, K., Tajima, N. A case of acquired deficiency of pituitary G.H., PRL and TSH, associated with T1D mellitus. Endocr. J. 2004, 51: 287-93.
82. MacFarlane, I.A., Sheppard, M.C., Black, E.G., Gilbey, S., Wright, A.D. The hypothalamic-pituitary-thyroid axis in T1D: influence of diabetic metabolic control. Acta Endocrinol. (Copenh.) 1984, 106: 92-6.
83. Gurr, W., Yavari, R., Wen, L., Shaw, M., Mora, C., Christa, L., Sherwin, R.S. A Reg family protein is overexpressed in islets from a patient with new-onset T1D and acts as T-cell autoantigen in NOD mice. Diabetes 2002, 51: 339-46.
84. Banchuin, N., Boonyasrisawat, W., Pulsawat, P., Vannasaeng, S., Deerochanawong, C., Sriussadaporn, S., Ploybutr, S., Pasurakul, T., Yenchitsomanus, P. No abnormalities of reg1 alpha and reg1 beta gene associated with diabetes mellitus. Diabetes Res. Clin. Pract. 2002, 55: 105-11.
85. Planas, R., Alba, A., Carrillo, J., Puertas, M.C., Ampudia, R., Pastor, X., Okamoto, H., Takasawa, S., Gurr, W., Pujol-Borrel, R., Verdaguer, J., Vives-Pi, M. Reg (regenerating) gene overexpression in islets from non-obese diabetic mice with accelerated diabetes: role of IFNbeta. Diabetologia 2006, 49: 2379-87.
86. Gurr W., Shaw, M., Li Y., Sherwin, R. RegII is a beta-cell protein and autoantigen in diabetes of NOD mice. Diabetes 2007, 56: 34-40.
87. Fraley, G.S., Scarlett, J.M., Shimada, I., Teklemichael, D.N., Acohido, B.V., Clifton, D.K., Steiner, R.A. Effects of diabetes and insulin on the expression of galanin-like peptide in the hypothalamus of the rat. Diabetes 2004, 53: 1237-42.
88. Stoyanovitch, A.G., Johnson, M.A., Clifton, D.K., Steiner, R.A., Fraley, G.S. Galanin-like peptide rescues reproductive function in the diabetic rat. Diabetes 2005, 54: 2471-6.
89. Itoh, Y., Kawamata, Y., Harada, M, Kobayashi, M., Fujii, R., Fukusumi, S., Ogi, K., Hosoya, M., Tanaka, Y., Uejima, H., Tanaka, H., Maruyama, M., Satoh, R., Okubo, S., Kizawa, H., Komatsu, H., Matsumura, F., Noguchi, Y., Shinohara, T., Hinuma, S., Fujisawa, Y., Fujino, M. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature 2003, 422: 173-6.
90. Kalis, M., Levéen, P., Lyssenko, V., Almgren, P., Groop, L., Cilio, C.M. Variants in the FFAR1 gene are associated with beta cell function. PLoS ONE 2007, 2: e1090.
91. Schumann, D.M., Maedler, K., Franklin, I., Konrad, D., Størling, J., Böni-Schnetzler, M., Gjinovci, A., Kurrer, M.O., Gauthier, B.R., Bosco, D., Andres, A., Berney, T., Greter, M., Becher, B., Chervonsky, A.V., Halban, P.A., Mandrup-Poulsen, T., Wollheim, C.B., Donath, M.Y. The Fas pathway is involved in pancreatic beta cell secretory function. Proc. Natl. Acad. Sci. USA 2007, 104: 2861-6.
92. Rudofsky, G. Jr., Schroedter, A., Schlotterer, A., Voron'ko, O.E., Schlimme, M., Tafel, J., Isermann, B.H., Humpert, P.M., Morcos, M., Bierhaus, A., Nawroth, P.P., Hamann, A. Functional polymorphisms of UCP2 and UCP3 are associated with a reduced prevalence of diabetic neuropathy in patients with TID. Diabetes Care 2006, 29: 89-94.
93. Emre, Y., Hurtaud, C., Karaca, M., Nubel, T., Zavala, F., Ricquier, D. Role of uncoupling protein UCP2 in cell-mediated immunity: how macrophage-mediated insulitis is accelerated in a model of autoimmune diabetes. Proc. Natl. Acad. Sci. USA 2007, 104: 19085-90.
94. Gorin, Y., Block, K., Hernandez, J., Bhandari, B., Wagner, B., Barnes, J.L., Abboud, H.E. Nox4 NAD(P)H oxidase mediates hypertrophy and fibronectin expression in the diabetic kidney. J. Biol. Chem. 2005, 280: 39616-26.
95. Mi, Q.S., Meagher, C., Delovitch, T.L. CD1d-restricted NKT regulatory cells: functional genomic analyses provide new insights into the mechanisms of protection against T1D. Novartis Found. Symp. 2003, 252: 146-60 discussion 160-4. 203-10.
96. Nolsøe, R.L., Pociot, F., Novick, D., Rubinstein, M., Kim, S.H., Dinarello, C.A., Mandrup-Poulsen, T. Mutation scan of a T1D candidate gene: the human interleukin-18 binding protein gene. Ann. N. Y. Acad. Sci. 2003, 1005: 332-9.
97. Wang, Z., Oh, E., Thurmond, D.C. Glucose-stimulated Cdc42 signaling is essential for the second phase of insulin secretion. J. Biol. Chem. 2007, 282: 9536-46.
98. van Beelen, A.J., Zelinkova, Z., Taanman-Kueter, E.W., Muller, F.J., Hommes, D.W., Zaat, S.A., Kapsenberg, M.L., de Jong, E.C. Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells. Immunity 2007, 27: 660-9.
99. Abbott, D.W., Wilkins, A., Asara, J.M., Cantley, L.C. The Crohn's disease protein, NOD2, requires RIP2 in order to induce ubiquitinylation of a novel site on NEMO. Curr. Biol. 2004, 14: 2217-27.
100. Miwa, T., Maldonado, M.A., Zhou, L., Sun, X., Luo, H.Y., Cai, D., Werth, V.P., Madaio, M.P., Eisenberg, R.A., Song, W.C. Deletion of decay-accelerating factor (CD55) exacerbates autoimmune disease development in MRL/lpr mice. Am. J. Pathol. 2002, 161: 1077-86.
101. Herr, C., Smyth, N., Ullrich, S., Yun, F., Sasse, P., Hescheler, J., Fleischmann, B., Lasek, K., Brixius, K., Schwinger, R.H., Fässler, R., Schröder, R., Noegel, A.A. Loss of annexin A7 leads to alterations in frequency-induced shortening of isolated murine cardiomyocytes. Mol. Cell. Biol. 2001, 21: 4119-28
102. Zipris, D., Lien, E., Nair, A., Xie, J.X., Greiner, D.L., Mordes, J.P., Rossini, A.A. TLR9-signaling pathways are involved in Kilham rat virus-induced autoimmune diabetes in the biobreeding diabetes-resistant rat. J. Immunol. 2007, 178: 693-701.
103. Mitchell, K.J., Tsuboi, T., Rutter, G.A. Role for plasma membrane-related Ca2+-ATPase-1 (ATP2Cl) in pancreatic beta-cell Ca2+ homeostasis revealed by RNA silencing. Diabetes 2004, 53: 393-400.
104. Greenbaum, C.J., Prigeon, R.L., D'Alessio, D.A. Impaired beta-cell function., incretin effect., and glucagon suppression in patients with T1D who have normal fasting glucose. Diabetes 2002, 51: 951-7.
105. Madsbad, S., Moody, A.J. Immunoreactive gastric inhibitory polypeptide response to a meal during the first eighteen months after diagnosis of type 1 (insulin dependent) diabetes mellitus. J. Clin. Endocrinol. Metab. 1985, 60: 120-5.
106. van Dam, E.W., Dekker, J.M., Lentjes, E.G., Romijn, F.P., Smulders, Y.M., Post W.J., Romijn, J.A., Krans, H.M. Steroids in adult men with T1D: a tendency to hypoganadism. Diabetes Care 2003, 26: 1812-8.
107. Holly, J.M., Dunger, D.B., al-Othman, S.A., Savage, M.O., Wass, J.A. Sex hormone binding globulin levels in adolescent subjects with diabetes mellitus. Diabetes Med. 1992, 9: 371-4.
108. Abke, S., Neumeier, M., Weigert, J., Wehrwein, G., Eggenhofer, E., Schäffler, A., Maier, K., Aslanidis, C., Schölmerich, J., Buechler, C. Adiponectin-induced secretion of interleukin-6 (IL-6)., monocyte chemotactic protein-1 (MCP-1, CCL2) and interleukin-8 (IL-8, CXCL8) is impaired in monocytes from patients with type I diabetes. Cardiovasc, Diabetol. 2006, 5: 17.
109. Hanifi-Moghaddam, P., Kappler, S., Seissler, J., Müller-Scholze, S., Martin, S., Roep, B.O., Strassburger, K., Kolb, H., Schloot, N.C. Altered chemokine levels in individuals at risk of T1D mellitus. Diabetes Med, 2006, 23: 156-63.
110. Cantor, J., Haskins, K. Recruitment and activation of macrophages by pathogenic CD4 T cells in T1D: evidence for involvement of CCR8 and CCL1. J. Immunol. 2007, 179: 5760-7.
111. Matos, M., Park, R., Mathis, D., Benoist C. Progression to islet destruction in a cyclophosphamide-induced transgenic model: a microarray overview. Diabetes 2004, 53: 2310-21.
112. Meagher, C., Arreaza, G., Peters, A., Strathdee, C.A., Gilbert, P.A., Mi, Q.S., Santamaria, P., Dekaban, G.A., Delovitch, T.L. CCL4 protects from TID by altering islet beta-cell-targeted inflammatory responses. Diabetes 2007, 56: 809-17.
113. Camacho, S.A., Heath, W.R., Carbone, F.R., Sarvetnick, N., LeBon, A., Karlsson, L., Peterson, P.A., Webb, S.R. A key role for ICAM-1 in generating effector cells mediating inflammatory responses. Nat. Immunol. 2001, 2: 523-9.
114. Johannesen, J., Pie, A., Pociot, F., Kristiansen, O.P., Karlsen, A.E., Nerup, J. Danish Study Group of Diabetes in Childhood. The Danish Insulin-dependent Diabetes Mellitus Epidemiology and Genetics Group. Linkage of the human inducible nitric oxide synthase gene to T1D. J. Clin. Endocrinol. Metab. 2001, 86: 2792-6.
115. Johannesen, J., Pociot, F., Kristiansen, O.P., Karlsen, A.E., Nerup J DIEGG and DSGD. Danish IddM Epidemiology and Genetics Group. Danish Study Group of Diabetis in Childhood. No evidence for linkage in the promoter region of the inducible nitric oxide synthase gene (NOS2) in a Danish T1D population. Genes Immun. 2000, 1: 362-6.
116. In't Veld, P., Lievens, D., De Grijse, J., Ling, Z., Van, der, Auwera, B., Pipeleers-Marichal, M., Gorus, F., Pipeleers, D. Screening for insulitis in adult autoantibody-positive organ donors. Diabetes 2007, 56(9): 2400-4.
117. Razavi, R., Chan, Y., Afifiyan, F.N., Liu, X.J., Wan X., Yantha, J., Tsui, H., Tang, L., Tsai, S., Santamaria, P., Driver, J.P., Serreze, D., Salter, M.W., Dosch, H.M. TRPV1+ sensory neurons control beta cell stress and islet inflammation in autoimmune diabetes. Cell 2006, 127: 1123-35.
118. Accardo-Palumbo, A., Triolo, G., Giardina, E., Carbone, M.C., Ferrante, A, Triolo, G. Detection of anti-myeloperoxidase antibodies in the serum of patients with T1D mellitus. Acta Diabetol. 1996, 33: 103-7.
119. Ivakine, E.A., Gulban, O.M., Mortin-Toth, S.M., Wankiewicz, E., Scott, C., Spurrell, D., Canty, A., Danska, J.S. Molecular genetic analysis of the Idd4 locus implicates the IFN response in T1D susceptibility in nonobese diabetic mice. J. Immunol. 2006, 176: 2976-92.
120. Xu, Z.G., Li, S.L., Lanting, L., Kim, Y.S., Shanmugam, N., Reddy, M.A., Natarajan, R. Relationship between 12/15-lipoxygenase and COX-2 in mesangial cells: potential role in diabetic nephropathy. Kidney Int 2006, 69: 512-9.
121. Saito, T., Okada, S., Yamada, E., Ohshima, K., Shimizu, H., Shimomura, K., Sato, M., Pessin, J.E., Mori, M. Syntaxin 4 and Synip (tyntaxin 4 interacting protein) regulate insulin secretion in the pancreatic beta HC-9 cell. J. Biol. Chem. 2003, 278, 36718-25.
122. Wang, C., Fang, Q., Zhang, R., Lin, X., Xiang, K. Scanning for MODY5 gene mutations in Chinese early onset or multiple affected diabetes pedigrees. Acta Diabetol. 2004, 41: 137-45.
123. Carbone, I., Cotellessa, M., Barella, C., Minetti, C., Ghiggeri, GM., Caridi, G., Perfumo, F., Lorini, R. A hepatocyte nuclear factor-1beta (MODY-5) gene mutation in an Italian family with renal dysfunctions and early-onset diabetes. Diabetologia 2002 45: 153-4.
124. Lau, J., Böjesson, A., Holstad, M., Sandler, S. Prolactin regulation of the expression of TNF-alpha, IFN-gamma and IL-10 by splenocytes in murine multiple low dose streptozotocin diabetes. Immunol. Lett. 2006, 102: 25-30.
125. Holstad, M., Sandler, S. Prolactin protects against diabetes induced by multiple low doses of streptozotocin in mice. J. Endocrinol. 1999, 163: 229-34.
126. Nguyen, T.Q., Chon, H., van, Nieuwenhoven, F.A., Braam, B., Verhaar, M.C., Goldschmeding, R. Myofibroblast progenitor cells are increased in number in patients with T1D and press less bone morphogenetic protein 6: a clue to adverse tissue remodelling? Diabetologia 2006, 49: 1039-48.
127. Eckenrode, S.E., Ruan, Q.G., Collins, C.D., Yang, P., McIndoe, R.A., Muir, A., She, J.X. Molecular pathways altered by insulin b9-23 immunization. Ann. N. Y. Acad. Sci. 2004, 1037: 175-85.
128. Hussain, K. Insights in congenital hyperinsulinism. Endocr. Dev. 2007 11: 106-21.
129. Tanizawa, Y., Nakai, K., Sasaki, T., Anno, T., Ohta, Y., Inoue, H., Matsuo, K., Koga, M., Funikawa, S., Oka, Y. Unregulated elevation of glutamate dehydrogenase activity induces glutamine-stimulated insulin secretion: identification and characterization of a GLUD1 gene mutation and insulin secretion studies with MIN6 cells overexpressing the mutant glutamate dehydrogenase. Diabetes 2002, 51: 712-7.
130. International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), Harley, J. B., Alarcon - Riquelme. M.E., Criswell, L.A., Jacob, C.O., Kimberly, R.P., Moser, K.L.,Tsao, B.P., Vyse, T.J., Langefeld, C.D. Gcnome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KLAA1542 and other loci. Nat. Genet. 2008, 40: 204-10.
131. Wilber, A., O'Connor, T.P., Lu, M.L., Karimi, A., Schneider, M.C. Dnase113 deficiency in lupus-prone MRL and NZB/W F1 mice. Clin. Exp. Immunol. 2003, 134: 46-52.
132. Burkhardt, B.R., Greene, S.R., White, P., Wong, R.K., Brestelli, J.E., Yang J., Robert, C.E., Brusko, T.M., Wasserfall, C.H., Wu, J., Atkinson, M.A., Gao, Z., Kaestner, K.H., Wolf BA. PANDER-induced cell-death genetic networks in islets reveal central role for caspase-3 and cyclin-dependent kinase inhibitor 1A (p21). Gene 2006, 369: 134-41.
133. Kauri, L.M., Wang, G.S., Patrick, C., Bareggi, M., Hill, D.J., Scott, F.W. Increased islet neogenesis without increased islet mass precedes autoimmune attack in diabetes-prone rats. Lab. Invest. 2007, 87: 1240-51.
134. Chun, T., Aldrich, C.J., Baldeón, M.E., Kawczynski, L.V., Soloski, M.J., Gaskins, H.R. Constitutive and regulated expression of the class IB molecule Qa-1 in pancreatic beta cells. Immunology 1998, 94: 64-71.
135. Hashimoto, M., Nakamura, N., Obayashi, H., Kimura, F., Moriwaki, A., Hasegawa, G., Shigeta, H., Kitagawa, Y., Nakano, K., Kondo, M., Ohta, M., Nishimura, M. Genetic contribution of the BAT2 gene microsatellite polymorphism to the age-at-onset of insulin-dependent diabetes mellitus. Hum. Genet. 1999, 105: 197-9.
136. Richter, S., Shih, D.Q., Pearson, E.R., Wolfrum, C., Fajans, S.S., Hattersley, A.T., Stoffel, M. Regulation of apolipoprotein M gene expression by MODY3 gene hepatocyte nuclear factor-I alpha: haploinsufficiency is associated with reduced serum apolipoprotein M levels. Diabetes 2003, 52: 2989-95.
137. Chistiakov, D.A., Seryogin, Y.A., Turakulov, R.I., Savost'anov, K.V., Titovich, E.V., Zilberman, L.I., Kuraeva, T.L., Dedov II., Nosikov,V.V. Evaluation of IDDM8 susceptibility locus in a Russian simplex family data set. J. Autoimmun. 2005, 24: 243-50.
138. Strokov, I.A., Bursa, T.R., Drepa, O.I., Zotova, E.V., Nosikov, V.V., Ametov, A.S. Predisposing genetic factors for diabetic polyneuropathy in patients with T1D: a population-based case-control study. Acta Diabetol. 2003, 40: S375-9.
139. McCann, J.A., Xu, Y.Q., Frechette, R., Guazzarotti, L., Polychronakos C. The insulin-like growth factor-II receptor gene is associated with T1D: evidence of a maternal effect. J. Clin. Endocrinol. Metab. 2004, 89: 5700-6.
140. Klöting, N., Klöting, I., Jack, R.S. CD14 triggers autoimmune T1D in the NOD mouse. Diabetologia 2004, 47: 151-2.
141. Kubosaki, A., Gross S., Miura, J., Saeki, K., Zhu, M., Nakamura, S., Hendriks, W., Notkins, A.L. Targeted disruption of the IA-2beta gene causes glucose intolerance and impairs insulin secretion but does not prevent the development of diabetes in NOD mice. Diabetes 2004, 53: 1684-91.
142. Irie, J., Reck, B., Wu, Y., Wicker, L.S., Howlett, S., Rainbow, D., Feingold, E., Ridgway, W.M. Genome-wide microarray expression analysis of CD4+ T cells from nonobese diabetic congenic mice identifies Cd55 (Daf1) and Acadl as candidate genes tor type 1 diabetes. J. Immunol. 2008, 180: 1071-9
143. Kawamura, Y., Tanaka, Y., Kawamori, R., Maeda, S. Overexpression of Kruppel-like factor 7 regulates adipocytokine gene expressions in human adipocytes and inhibits glucose-induced insulin secretion in pancreatic beta-cell line. Mol. Endocrinol. 2006, 20: 844-56.
144. Rani, S., Clynes, M., O'Driscoll, L. Detection of amplifiable mRNA extracellular to insulin-producing cells: potential for predicting beta cell mass and function. Clin. Chem. 2007, 53: 1936-44.
145. Swift G.H., Liu, Y., Rose, S.D., Bischot L.J., Steelman, S., Buchberg, A.M., Wright, C.V., MacDonald, R.J. An endocrine-exocrine switch in the activity of the pancreatic homeodomain protein PDX1 through formation of a trimeric complex with PBX1b and MRG1 (MEIS2). Mol. Cell. Biol. 1999, 18: 5109-20.
146. Otonkoski, T., Jiao, H., Kaminen-Ahola, N., Tapia-Paez, I., Ullah, M.S., Parton, L.E., Schuit, F., Quintens, R., Sipilä, I., Mayatepek, E., Meissner, T., Halestrap, A.P., Rutter, G.A., Kere, J. Physical exercise-induced hypoglyoemia caused by failed silencing of monocarboxylate transporter 1 in pancreatic beta cells. Am. J. Hum. Genet. 2007, 81: 467-74.
147. Rulifson, I.C., Karnik, S.K., Heiser, P.W., ten Berge, D., Chen, H., Gu, X., Taketo, M.M., Nusse, R., Hebrok, M., Kim, SK. Wnt signaling regulates pancreatic beta cell proliferation. Proc. Natl. Acad. Sci. USA 2007, 104: 6247-52.
148. Zhang, J., Tokui, Y.; Yamagata, K., Kozawa, J., Sayama K., Iwahashi, H., Okita, K. Miuchi, M., Konya, H., Hamaguchi, T., Namba, M., Shimomura, I., Miyagawa, J.I. Continuous stimulation of human glucagon-like peptide-1 (7-36) amide in a mouse model (NOD) delays onset of autoimmune type 1 diabetes. Diabetologia 2007; 50: 1900-9.
149. Hardikar, A.A., Marcus-Samuels, B., Geras-Raaka, E., Raaka, B.M., Gershengorn, M.C. Human pancreatic precursor cells secrete FGF2 to stimulate clustering into hormone-expressing islet-like cell aggregates. Proc. Natl. Acad. Sci. USA 2003, 100: 7117-22.
150. Irie, J., Wu, Y., Kachapati, K., Mittler, R.S., Ridgway, W.M. Modulating protective and pathogenic CD4+ subsets via CD 137 in type 1 diabetes. Diabetes 2007, 56: 186-96.
151. Iguchi, H., Urashima, Y., Inagaki, Y., Ikeda, Y., Okamura, M., Tanaka, T., Uchida, A., Yamamoto, T.T., Kodama, T., Sakai, J. 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. 2007, 282: 19052-61.
152. Park, K.G., Lee, KM., Seo, H.Y., Suh, J.H., Kim, H.S., Wang, L., Won, K,C., Lee, H.W., Park, J.Y., Lee, K.U., Kim, J.G., Kim, B.W., Choi, H.S., Lee, I.K. Glucotoxicity in the INS-1 rat insulinoma cell line is mediated by the orphan nuclear receptor small heterodimer partner. Diabetes 2007, 56: 431-7.
153. Zhang, H., Ackermann, A.M., Gusarova, G.A., Lowe, D., Feng, X., Kopsombut, U.G., Costa, R.H., Gannon, M. The FoxM1 transcription factor is required to maintain pancreatic beta-cell mass. Mol. Endocrinol. 2006, 20: 1853-66.
154. Rosen, E.D., Kulkarni, R.N., Surraf P., Ozcan, U., Okada, T., Hsu, C.H., Eisenman, D., Magnuson, M.A., Gonzalez, F.J., Kahn, C.R., Spiegelman, B.M. Targeted elimination of peroxisome proliferator-activated receptor gamma in beta cells leads to abnormalities in islet mass without compromising glucose homeostasis. Mol. Cell. Biol. 2003; 23: 7222-9.
155. Garofalo, R.S., Orena, S.J., Rafidi, K., Torchia, A.J., Stock, J.L., Hildebrandt, A.L., Coskran, T., Black, S.C., Brees, D.J., Wicks, J.R., McNeish, J.D., Coleman, K.G. Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB beta. J. Clin. Invest. 2003, 112: 197-208.
156. Kayo, T., Sawada, Y., Suda, M., Konda, Y., Izumi, T., Tanaka, S., Shibata, H., Takeuchi, T. Proprotein-processing endoprotease furin controls growth of pancreatic beta-cells. Diabetes 1997, 46: 1296-304.
157. Guota, R.K.,,Gao, N., Gorski, R.K., White, P., Hardy, O.T., Rafiq, K., Brestelli, J.E., Chen, G., Stoeckert, C.J. Jr., Kaestner, K.H. Expansion of adult beta-cell mass in response to increased metabolic demand is dependent on HNF-4alpha. Genes Dev. 2007, 21: 756-69.
158. Frödin, M., Sekine, N., Roche, E., Filloux, C., Prentki, M., Wollheim, CB., Van, Obberghen, E. Glucose, other secretagogues, and nerve growth factor stimulate mitogen-activated protein kinase in the insulin-secreting beta-cell line, INS-1. J. Biol. Chem. 1995, 270: 7882-9.
159. Giulietti, A., Gysemans C., Stoffels, K., van, Etten, E., Decallonne, B., Overbergh, L., Bouillon, R., Mathieu, C. Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice. Diabetologia 2004, 47: 451-62.
160. Nakamura, Y., Kaneto, H., Miyatsuka J., Matsuoka, TA., Matsuhisa, M., Node, K., Hori, M., Yamasaki, Y. Marked increase of insulin gene transcription by suppression of the Rho/Rho-kinase pathway. Biochem. Biophys. Res. Commun. 2006, 350: 68-73.
161. Klinger, S., Poussin, C., Debril, M.B., Dolci, W., Halban, P.A., Thorens, B. Increasing GLP-1-induced {beta}-cell proliferation by silencing the negative regulators of signaling CREM {alpha} and DUSP14. Diabetes 2008, 57: 584-93.
162. Kagami-Takasugi, M., Katsumata, N., Tanaka, T., Tajima, T., Fujieda, K. Molecular genetic analysis of MODY candidate genes in Japanese patients with non-obese juvenile onset diabetes mellitus. J. Pediatr. Endocrinol. Metab. 2006, 19: 143-8.
163. Pearson, E.R., Badman, M.K., Lockwood, C.R., Clark, P.M., Ellard, S., Bingham, C., Hattersley, A.T. Contrasting diabetes phenotypes associated with hepatocyte nuclear factor-1alpha and - 1beta mutations. Diabetes Care 2004, 27: 1102-7.
164. Peng, R.H., Pack, E., Xia, C.Q., Tennysoli, N., Clare-Salzier, M.J. Heightened interferon-alpha/beta response causes myeloid cell dys-function and promotes T1D pathogenesis in NOD mice. Ann. N. Y. Acad. Sci. 2006, 1079: 99-102.
165. Zacher, T., Kneff, I., Rascher, W., Kalden,.J.R., Wassmuth, R. Characterization of monocyte-derived dendritic cells in recent-onset diabetes mellitus type 1. Clin. Immunol. 2002, 105: 17-24.
166. Pascoe, L., Tura, A., Patel, S.K., Ibrahim, I.M., Ferrannini, E., Zeggini, E., Weedon, M.N., Mari, A., Hattersley, A.T., McCarthy, M.I., Frayling, T.M., Walker, M. RISC Consortium U.K. Type 2 Diabetes Genetics Consortium. Common variants of the novel type 2 diabetes genes CDKAL1 and HHEX/IDE are associated with decreased pancreatic beta-cell function. Diabetes 2007, 56: 3101-4.
167. Goulley, J., Dahl, U., Baeza, N., Mishina, Y., Edlund, H. BMP4-BMPR1A signaling in beta cells is required for and augments glucose-stimulated insulin secretion. Cell. Metab. 2007, 5: 207-19.
168. Budowle, B., Roseman, J.M., Go, R.C., Barger, B.O., Acton, R.T. The complement component C4 in black Americans with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1984, 26: 166-8.
169. Kawaguchi, Y., Ikegami, H., Fukuda, M., Takekawa, K., Fujioka, Y., Fujisawa, T., Ueda, H., Ogihara, T. Absence of association of TAP and LMP genes with type 1 (insulin-dependent) diabetes mellitus. Life Sci. 1994, 54: 2049-53.
170. Rau, H., Nicolay, A., Donner, H., Usadel, K.H., Badenhoop, K. Polymorphisms of TAP1 and TAP2 genes in German patients with type 1 diabetes mellitus. Eur. J. Immunogenet. 1997, 24: 229-36.
171. Payne, F., Smyth, D.J., Pask, R,, Cooper, J.D., Masters, J., Wang, W.Y., Godfrey, L.M., Bowden, G., Szeszko, J., Smink, L.J., Lam, A.C., Burren, O., Walker, N.M., Nutland, S., Rance, H., Undlien, D.E., Ronningen, K.S., Guja, C., Ionescu-Tirgovişte, C., Todd, J.A., Twells, R.C. No evidence for association of the TATA-box binding protein glutamine repeat sequence or the flanking chromosome 6q27 region with type 1 diabetes. Biochem. Biophys. Res. Commun. 2005, 331: 435-41.
172. Lu, H., Kraut, D.,,Gerstenfeld, L.C., Graves, D.T. Diabetes interferes with the bone formation by affecting the expression of transcription factors that regulate osteoblast differentiation. Endocrinology 2003, 144: 346-52.
173. Herbon, N., Wemer, M., Braig, C., Gohlke, H., Dütsch, G., Illig, T., Altmüller, J., Hampe, J., Lantermann, A., Schreiber, S., Bonifacio, E., Ziegler, A., Schwab, S., Wildenauer, D., van den Boom, D., Braun, A., Knapp, M., Reitmeir, P., Wjst, M. High-resolution SNP scan of chromosome 6p2l in pooled samples from patients with complex diseases. Genomics 2003, 81: 510-8.
174. Undlien, D.E., Thorsby, E. HLA associations in type 1 diabetes: merging genetics and immunology. Trends Immunol 2001, 22: 467-469.
175. Al-Kateb, H., Mirea, L., Xie, X., Sun, L., Liu, M., Chen, H, Bull, S.B., Boright, A.P., Paterson, A.D., DCCT/EDIC Research Group. Multiple variants in vascular endothelial growth factor (VEGFA) are risk factors for time to severe retinopathy in type 1 diabetes: the DCCT/EDIC genetics study. Diabetes 2007, 56: 2161-8.
176. Yamashita, T., Hamaguchi, K., Kusuda, Y., Kimura, A., Sakata, T., Yoshimatsu, H. IKBL promoter polymorphism is strongly associciated with resistance to type 1 diabetes in Japanese. Tissue Antigens 2004, 63: 223-30.
177. Lindholm, E., Bakhtadze, E., Sjögren, M., Cilio, C.M., Agardh, E., Groop, L., Agardh, C.D. The -374 T/A polymorphism in the gene encoding RAGE is associated with diabetic nephropathy and retinopathy in type 1 diabetic patients. Diabetologia 2006, 49: 2745-55.
178. Anastasi, E., Campese, A.F., Bellavia, D., Bulotta, A., Balestri, A., Pascucci, M., Checquolo, S., Gradini, R., Lendahl, U., Frati, L., Gulino, A., Di Mario, U., Screpanti, I. Expression of activated Notch3 in transgenic mice enhances generation of T regulatory cells and protects against experimental autoimmune diabetes. J. Immunol. 2003, 171: 4504-11.
179. Davoodi-Semiromi, A., Laloraya, M., Kumar, G.P., Purohik S., Jha, R.K., She, J.X. A mutant Stat5b with weaker DNA binding affinity defines a key defective pathway in nonobese diabetic mice. J. Biol Chem. 2004, 279: 11553-61.
180. Roach, J.C., Deutsch, K., Li, S., Siegel, A.F., Beluis, L.M., Einhaus, D.C., Sheridan, C.M., Glusman, G., Hood, L., Lernmark, A., Janer, M., Swedish Childhood Diabetes Study Group Diabetes Incidence in Sweden Study Group. Genetic mapping at 3-kilobase resolution reveals inositol 1,4,5-triphosphate receptor 3 as a risk factor for type 1 diabetes in Sweden. Am J. Hum Genet. 2006, 79: 614-27.
181. Bernal-Mizrachi, E., Wice, B., Inoue, H., Permutt, M.A. Activation of serum response factor in the depolarization induction of Egr-1 transcription in pancreatic islet beta-cells. J. Biol. Chem. 2000, 275: 25681-9.