Subscribe to RSS
DOI: 10.1055/s-2008-1080898
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York
Proteomic Profiling of β-cells Using a Classical Approach – Two-dimensional Gel Electrophoresis
Publication History
received 15.04.2008
first decision 15.05.2008
accepted 15.05.2008
Publication Date:
05 September 2008 (online)
Abstract
Proteomics has rapidly become a major field of research in biology and medicine. Its main aim is to obtain a global overview of the expression pattern of proteins and their relationship in any given condition of a biological system. This knowledge is of particular interest to elucidate the pathogenesis of complex disorders, such as diabetes. Separation of proteins by two-dimensional gel electrophoresis (2-DE) followed by mass spectrometry (MS) for their identification is perhaps the most widely used proteomic approach. In this review we have focused our attention on studies that have taken advantage of these methodologies to investigate the proteome of pancreatic islets, β-cells and insulinoma cells in different conditions. As β-cells of the pancreatic islets produce and secrete insulin, the main hormone for control of glucose homeostasis, these analyses may help to elucidate the mechanisms regulating insulin secretion and the development of various forms of diabetes, as well as to identify drug targets for therapeutic approaches.
Key words
beta cells - diabetes - autoimmunity - proteomics - glucose regulation - two-dimensional differential gel electrophoresis
References
- 1 Aebersold R, Mann M. Mass spectrometry-based proteomics. Nature. 2003; 422 198-207
- 2 Aggarwal K, Choe LH, Lee KH. Shotgun proteomics using the iTRAQ isobaric tags. Brief Funct Genomic Proteomic. 2006; 5 112-120
- 3 Ahmed M, Bergsten P. Glucose-induced changes of multiple mouse islet proteins analysed by two-dimensional gel electrophoresis and mass spectrometry. Diabetologia. 2005; 48 477-485
- 4 Ahmed M, Forsberg J, Bergsten P. Protein profiling of human pancreatic islets by two-dimensional gel electrophoresis and mass spectrometry. J Proteome Res. 2005; 4 931-940
- 5 Alarcon C, Lincoln B, Rhodes CJ. The biosynthesis of the subtilisin-related proprotein convertase PC3, but no that of the PC2 convertase, is regulated by glucose in parallel to proinsulin biosynthesis in rat pancreatic islets. J Biol Chem. 1993; 268 4276-4280
- 6 Alban A, David SO, Bjorkesten L, Andersson C, Sloge E, Lewis S, Currie I. A novel experimental design for comparative two-dimensional gel analysis: two-dimensional difference gel electrophoresis incorporating a pooled internal standard. Proteomics. 2003; 3 36-44
- 7 Andersen HU, Fey SJ, Larsen PM, Nawrocki A, Hejnaes KR, Mandrup-Poulsen T, Nerup J. Interleukin-1beta induced changes in the protein expression of rat islets: a computerized database. Electrophoresis. 1997; 18 2091-2103
- 8 Beith JL, Alejandro EU, Johnson JD. Insulin stimulates primary {beta}-cell proliferation via Raf-1 Kinase. Endocrinology. 2008;
- 9 Bordin S, Amaral ME, Anhe GF, Delghingaro-Augusto V, Cunha DA, Nicoletti-Carvalho JE, Boschero AC. Prolactin-modulated gene expression profiles in pancreatic islets from adult female rats. Mol Cell Endocrinol. 2004; 220 41-50
- 10 Brunner Y, Coute Y, Iezzi M, Foti M, Fukuda M, Hochstrasser DF, Wollheim CB, Sanchez JC. Proteomics analysis of insulin secretory granules. Mol Cell Proteomics. 2007; 6 1007-1017
- 11 Christensen UB, Larsen PM, Fey S, Karlsen AE, Pociot F, Nerup J, Sparre T. Different islet protein expression profiles during spontaneous diabetes development vs. allograft rejection in BB-DP rats. Autoimmunity. 2006; 39 315-321
- 12 Christensen UB, Larsen PM, Fey SJ, Andersen HU, Nawrocki A, Sparre T, Mandrup-Poulsen T, Nerup J. Islet protein expression changes during diabetes development in islet syngrafts in BB-DP rats and during rejection of BB-DP islet allografts. Autoimmunity. 2000; 32 1-15
- 13 D’Hertog W, Overbergh L, Lage K, Ferreira GB, Maris M, Gysemans C, Flamez D, Cardozo AK, den Bergh G Van, Schoofs L, Arckens L, Moreau Y, Hansen DA, Eizirik DL, Waelkens E, Mathieu C. Proteomics analysis of cytokine-induced dysfunction and death in insulin-producing INS-1E cells: new insights into the pathways involved. Mol Cell Proteomics. 2007; 6 2180-2199
- 14 Hoog CL de, Mann M. Proteomics. Annu Rev Genomics Hum Genet. 2004; 5 267-293
- 15 Donath MY, Schumann DM, Faulenbach M, Ellingsgaard H, Perren A, Ehses JA. Islet inflammation in type 2 diabetes: from metabolic stress to therapy. Diabetes Care. 2008; 31 ((Suppl 2)) S161-S164
- 16 Dowling P, O’Driscoll L, O’Sullivan F, Dowd A, Henry M, Jeppesen PB, Meleady P, Clynes M. Proteomic screening of glucose-responsive and glucose non-responsive MIN-6 beta cells reveals differential expression of proteins involved in protein folding, secretion and oxidative stress. Proteomics. 2006; 6 6578-6587
- 17 Falkner JA, Hill JA, Andrews PC. Proteomics FASTA archive and reference resource. Proteomics. 2008; 8 1756-1757
- 18 Fernandez C, Fransson U, Hallgard E, Spegel P, Holm C, Krogh M, Warell K, James P, Mulder H. Metabolomic and proteomic analysis of a clonal insulin-producing beta-cell line (INS-1 832/13). J Proteome Res. 2008; 7 400-411
- 19 Fujinaka Y, Takane K, Yamashita H, Vasavada RC. Lactogens promote beta cell survival through JAK2/STAT5 activation and Bcl-XL upregulation. J Biol Chem. 2007; 282 30707-30717
- 20 Gasteiger E, Gattiker A, Hoogland C, Ivanyi I, Appel RD, Bairoch A. ExPASy: The proteomics server for in-depth protein knowledge and analysis. Nucleic Acids Res. 2003; 31 3784-3788
- 21 Gorg A, Weiss W, Dunn MJ. Current two-dimensional electrophoresis technology for proteomics. Proteomics. 2004; 4 3665-3685
- 22 Greenman IC, Gomez E, Moore CE, Herbert TP. The selective recruitment of mRNA to the ER and an increase in initiation are important for glucose-stimulated proinsulin synthesis in pancreatic beta-cells. Biochem J. 2005; 391 291-300
- 23 Guest PC, Bailyes EM, Rutherford NG, Hutton JC. Insulin secretory granule biogenesis. Co-ordinate regulation of the biosynthesis of the majority of constituent proteins. Biochem J. 1991; 274 ((Pt 1)) 73-78
- 24 Guest PC, Rhodes CJ, Hutton JC. Regulation of the biosynthesis of insulin-secretory-granule proteins. Co-ordinate translational controls is exerted on some, but not all, granule matrix constituents. Biochem J. 1989; 257 431-437
- 25 Gygi SP, Corthals GL, Zhang Y, Rochon Y, Aebersold R. Evaluation of two-dimensional gel electrophoresis-based proteome analysis technology. Proc Natl Acad Sci USA. 2000; 97 9390-9395
- 26 Gygi SP, Rochon Y, Franza BR, Aebersold R. Correlation between protein and mRNA abundance in yeast. Mol Cell Biol. 1999; 19 1720-1730
- 27 Haab BB. Applications of antibody array platforms. Curr Opin Biotechnol. 2006; 17 415-421
- 28 Hamacher M, Marcus K, Stephan C, Klose J, Park YM, Meyer HE. HUPO Brain Proteome Project: toward a code of conduct. Mol Cell Proteomics. 2008a; 7 457
- 29 Hamacher M, Stephan C, Eisenacher M, Hardt T, Marcus K, Meyer HE. Maintaining standardization: an update of the HUPO Brain Proteome Project. Expert Rev Proteomics. 2008b; 5 165-173
- 30 Hinke SA, Hellemans K, Schuit FC. Plasticity of the beta cell insulin secretory competence: preparing the pancreatic beta cell for the next meal. J Physiol. 2004; 558 369-380
- 31 Hoogland C, Mostaguir K, Sanchez JC, Hochstrasser DF, Appel RD. SWISS-2DPAGE, ten years later. Proteomics. 2004; 4 2352-2356
- 32 Itoh N, Okamoto H. Translational control of proinsulin synthesis by glucose. Nature. 1980; 283 100-102
- 33 Jagerbrink T, Lexander H, Palmberg C, Shafqat J, Sharoyko V, Berggren PO, Efendic S, Zaitsev S, Jornvall H. Differential protein expression in pancreatic islets after treatment with an imidazoline compound. Cell Mol Life Sci. 2007; 64 1310-1316
- 34 Jensen J, Galsgaard ED, Karlsen AE, Lee YC, Nielsen JH. STAT5 activation by human GH protects insulin-producing cells against interleukin-1beta, interferon-gamma and tumour necrosis factor-alpha-induced apoptosis independent of nitric oxide production. J Endocrinol. 2005; 187 25-36
- 35 John NE, Andersen HU, Fey SJ, Larsen PM, Roepstorff P, Larsen MR, Pociot F, Karlsen AE, Nerup J, Green IC, Mandrup-Poulsen T. Cytokine- or chemically derived nitric oxide alters the expression of proteins detected by two-dimensional gel electrophoresis in neonatal rat islets of Langerhans. Diabetes. 2000; 49 1819-1829
- 36 Johnson JD, Bernal-Mizrachi E, Alejandro EU, Han Z, Kalynyak TB, Li H, Beith JL, Gross J, Warnock GL, Townsend RR, Permutt MA, Polonsky KS. Insulin protects islets from apoptosis via Pdx1 and specific changes in the human islet proteome. Proc Natl Acad Sci USA. 2006; 103 19575-19580
- 37 Jones P, Cote RG, Cho SY, Klie S, Martens L, Quinn AF, Thorneycroft D, Hermjakob H. PRIDE: new developments and new datasets. Nucleic Acids Res. 2008; 36 D878-883
- 38 Kaestner KH, Lee CS, Scearce LM, Brestelli JE, Arsenlis A, Le PP, Lantz KA, Crabtree J, Pizarro A, Mazzarelli J, Pinney D, Fischer S, Manduchi E, Stoeckert Jr CJ, Gradwohl G, Clifton SW, Brown JR, Inoue H, Cras-Meneur C, Permutt MA. Transcriptional program of the endocrine pancreas in mice and humans. Diabetes. 2003; 52 1604-1610
- 39 Knoch KP, Bergert H, Borgonovo B, Saeger HD, Altkruger A, Verkade P, Solimena M. Polypyrimidine tract-binding protein promotes insulin secretory granule biogenesis. Nat Cell Biol. 2004; 6 207-214
- 40 Knoch KP, Meisterfeld R, Kersting S, Bergert H, Altkruger A, Wegbrod C, Jager M, Saeger HD, Solimena M. cAMP-dependent phosphorylation of PTB1 promotes the expression of insulin secretory granule proteins in beta cells. Cell Metab. 2006; 3 123-134
- 41 Labriola L, Ferreira GB, Montor WR, Demasi MA, Pimenta DC, Lojudice FH, Genzini T, Goldberg AC, Eliaschewitz FG, Sogayar MC. Prolactin-induced changes in protein expression in human pancreatic islets. Mol Cell Endocrinol. 2007; 264 16-27
- 42 Larsen PM, Fey SJ, Larsen MR, Nawrocki A, Andersen HU, Kahler H, Heilmann C, Voss MC, Roepstorff P, Pociot F, Karlsen AE, Nerup J. Proteome analysis of interleukin-1beta-induced changes in protein expression in rat islets of Langerhans. Diabetes. 2001; 50 1056-1063
- 43 Luche S, Santoni V, Rabilloud T. Evaluation of nonionic and zwitterionic detergents as membrane protein solubilizers in two-dimensional electrophoresis. Proteomics. 2003; 3 249-253
- 44 Lv LL, Liu BC. High-throughput antibody microarrays for quantitative proteomic analysis. Expert Rev Proteomics. 2007; 4 505-513
- 45 Mandrup-Poulsen T. The role of interleukin-1 in the pathogenesis of IDDM. Diabetologia. 1996; 39 1005-1029
- 46 Marouga R, David S, Hawkins E. The development of the DIGE system: 2D fluorescence difference gel analysis technology. Anal Bioanal Chem. 2005; 382 669-678
- 47 Mazzarelli JM, White P, Gorski R, Brestelli J, Pinney DF, Arsenlis A, Katokhin A, Belova O, Bogdanova V, Elisafenko E, Gubina M, Nizolenko L, Perelman P, Puzakov M, Shilov A, Trifonoff V, Vorobjeva N, Kolchanov N, Kaestner KH, Stoeckert Jr CJ. Novel genes identified by manual annotation and microarray expression analysis in the pancreas. Genomics. 2006; 88 752-761
- 48 Nicolls MR, D’Antonio JM, Hutton JC, Gill RG, Czwornog JL, Duncan MW. Proteomics as a tool for discovery: proteins implicated in Alzheimer's disease are highly expressed in normal pancreatic islets. J Proteome Res. 2003; 2 199-205
- 49 Nielsen JH, Galsgaard ED, Moldrup A, Friedrichsen BN, Billestrup N, Hansen JA, Lee YC, Carlsson C. Regulation of beta-cell mass by hormones and growth factors. Diabetes. 2001; 50 ((Suppl 1)) S25-S29
- 50 O’Farrell PH. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975; 250 4007-4021
- 51 Ong SE, Mann M. Mass spectrometry-based proteomics turns quantitative. Nat Chem Biol. 2005; 1 252-262
- 52 Qiu L, List EO, Kopchick JJ. Differentially expressed proteins in the pancreas of diet-induced diabetic mice. Mol Cell Proteomics. 2005; 4 1311-1318
- 53 Ross PL, Huang YN, Marchese JN, Williamson B, Parker K, Hattan S, Khainovski N, Pillai S, Dey S, Daniels S, Purkayastha S, Juhasz P, Martin S, Bartlet-Jones M, He F, Jacobson A, Pappin DJ. Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol Cell Proteomics. 2004; 3 1154-1169
- 54 Rutter GA, Varadi A, Tsuboi T, Parton L, Ravier M. Insulin secretion in health and disease: genomics, proteomics and single vesicle dynamics. Biochem Soc Trans. 2006; 34 247-250
- 55 Sanchez JC, Chiappe D, Converset V, Hoogland C, Binz PA, Paesano S, Appel RD, Wang S, Sennitt M, Nolan A, Cawthorne MA, Hochstrasser DF. The mouse SWISS-2D PAGE database: a tool for proteomics study of diabetes and obesity. Proteomics. 2001; 1 136-163
- 56 Sanchez JC, Converset V, Nolan A, Schmid G, Wang S, Heller M, Sennitt MV, Hochstrasser DF, Cawthorne MA. Effect of rosiglitazone on the differential expression of diabetes-associated proteins in pancreatic islets of C57Bl/6 lep/lep mice. Mol Cell Proteomics. 2002; 1 509-516
- 57 Scearce LM, Brestelli JE, MacWeeney SK, Lee CS, Mazzarelli J, Pinney DF, Pizarro A, Stoeckert Jr CJ, Clifton SW, Permutt MA, Brown J, Melton DA, Kaestner KH. Functional genomics of the endocrine pancreas: the pancreas clone set and PancChip, new resources for diabetes research. Diabetes. 2002; 51 1997-2004
- 58 Schuit F, Flamez D, Vos A De, Pipeleers D. Glucose-regulated gene expression maintaining the glucose-responsive state of beta-cells. Diabetes. 2002; 51 ((Suppl 3)) S326-S332
- 59 Sparre T, Christensen UB, Mose Larsen P, Fey SJ, Wrzesinski K, Roepstorff P, Mandrup-Poulsen T, Pociot F, Karlsen AE, Nerup J. IL-1beta induced protein changes in diabetes prone BB rat islets of Langerhans identified by proteome analysis. Diabetologia. 2002; 45 1550-1561
- 60 Sparre T, Larsen MR, Heding PE, Karlsen AE, Jensen ON, Pociot F. Unraveling the pathogenesis of type 1 diabetes with proteomics: present and future directions. Mol Cell Proteomics. 2005; 4 441-457
- 61 Stanislaus R, Arthur JM, Rajagopalan B, Moerschell R, MacGlothlen B, Almeida JS. An open-source representation for 2-DE-centric proteomics and support infrastructure for data storage and analysis. BMC Bioinformatics. 2008; 9 4
-
62
Suckale J, Solimena M.
Pancreas islets in metabolic signaling – focus on the beta-cell.
, Frontiers in Bioscience in print:
- 63 Tillmar L, Carlsson C, Welsh N. Control of insulin mRNA stability in rat pancreatic islets. Regulatory role of a 3′-untranslated region pyrimidine-rich sequence. J Biol Chem. 2002; 277 1099-1106
- 64 Unlu M, Morgan ME, Minden JS. Difference gel electrophoresis: a single gel method for detecting changes in protein extracts. Electrophoresis. 1997; 18 2071-2077
- 65 Bergh G Van den, Arckens L. Fluorescent two-dimensional difference gel electrophoresis unveils the potential of gel-based proteomics. Curr Opin Biotechnol. 2004; 15 38-43
- 66 Bergh G Van den, Clerens S, Cnops L, Vandesande F, Arckens L. Fluorescent two-dimensional difference gel electrophoresis and mass spectrometry identify age-related protein expression differences for the primary visual cortex of kitten and adult cat. J Neurochem. 2003a; 85 193-205
- 67 Bergh G Van den, Clerens S, Vandesande F, Arckens L. Reversed-phase high-performance liquid chromatography prefractionation prior to two-dimensional difference gel electrophoresis and mass spectrometry identifies new differentially expressed proteins between striate cortex of kitten and adult cat. Electrophoresis. 2003b; 24 1471-1481
-
68 Lommel L, Moreau Y, Pipeleers D, Jonas J-C, Schuit F. mRNA profiling of pancreatic beta cells: investigating mechanisms of diabetes. In: Hofmann W-K (Ed),
Gene Expression Profiling by Microarrays: Clinical Implications . Cambridge University Press 2006: 187-211 - 69 Welsh M, Nielsen DA, MacKrell AJ, Steiner DF. Control of insulin gene expression in pancreatic beta-cells and in an insulin-producing cell line, RIN-5F cells. II. Regulation of insulin mRNA stability. J Biol Chem. 1985; 260 13590-13594
- 70 Westbrook JA, Yan JX, Wait R, Welson SY, Dunn MJ. Zooming-in on the proteome: very narrow-range immobilised pH gradients reveal more protein species and isoforms. Electrophoresis. 2001; 22 2865-2871
- 71 Wicksteed B, Alarcon C, Briaud I, Lingohr MK, Rhodes CJ. Glucose-induced translational control of proinsulin biosynthesis is proportional to preproinsulin mRNA levels in islet beta-cells but not regulated via a positive feedback of secreted insulin. J Biol Chem. 2003; 278 42080-42090
- 72 Wicksteed B, Uchizono Y, Alarcon C, MacCuaig JF, Shalev A, Rhodes CJ. A cis-element in the 5′ untranslated region of the preproinsulin mRNA (ppIGE) is required for glucose regulation of proinsulin translation. Cell Metab. 2007; 5 221-227
- 73 Xie X, Li S, Liu S, Lu Y, Shen P, Ji J. Proteomic analysis of mouse islets after multiple low-dose streptozotocin injection. Biochim Biophys Acta. 2008; 1784 276-284
- 74 Zhou G, Li H, DeCamp D, Chen S, Shu H, Gong Y, Flaig M, Gillespie JW, Hu N, Taylor PR, Emmert-Buck MR, Liotta LA, Petricoin 3rd EF, Zhao Y. 2D differential in-gel electrophoresis for the identification of esophageal scans cell cancer-specific protein markers. Mol Cell Proteomics. 2002; 1 117-124
Correspondence
M. Solimena
Experimental Diabetology
Fetscherstraße 74
01307 Dresden
Germany
Phone: +49/351/458 66 11
Fax: +49/351/458 63 30
Email: michele.solimena@tu-dresden.de