Skip to main content

Advertisement

Log in

Protein transduction technology offers a novel therapeutic approach for diabetes

  • Review article
  • Published:
Journal of Hepato-Biliary-Pancreatic Surgery

Abstract

Diabetes remains a major burden, with more than 200 million people affected worldwide, representing 6% of the population. New technology, known as protein transduction technology, has been recently developed. A variety of peptides, known as protein transduction domains or cell-penetrating peptides, have been characterized for their ability to translocate into live cells. There are numerous examples of biologically active full-length proteins and peptides that have been delivered to cells and tissues both in vitro and in vivo, suggesting new avenues for the treatment of several diseases. Some studies have shown that this technology is useful for the treatment of diabetes. In islet isolation and transplantation, cell-permeable peptides deliver anti-apoptotic molecules to protect islets. Another peptide provides immunosuppression for fully mismatched islet allografts in mice. These findings suggest that peptide drugs could lead to outcome improvement for pancreatic islet transplantation. In mice with type 2 diabetes, a cell-penetrating peptide markedly improves insulin resistance and ameliorates glucose tolerance. Moreover, the technology facilitates the differentiation of stem cells into insulin-producing cells. Protein transduction technology has opened up several possibilities for the development of new peptide/protein drugs for the treatment of diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. JP Boyle AA Honeycutt KM Narayan TJ Hoerger LS Geiss H Chen et al. (2001) ArticleTitleProjection of diabetes burden through 2050: impact of changing demography and disease prevalence in the U.S Diabetes Care 24 1936–40 Occurrence Handle11679460 Occurrence Handle1:STN:280:DC%2BD3MrntF2jsA%3D%3D

    PubMed  CAS  Google Scholar 

  2. InstitutionalAuthorNameThe Diabetes Control and Complications Trial Research Group (1993) ArticleTitleThe effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus N Engl J Med 329 977–86 Occurrence Handle10.1056/NEJM199309303291401

    Article  Google Scholar 

  3. UK Prospective (1998) ArticleTitleDiabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33) Lancet 352 837–53 Occurrence Handle10.1016/S0140-6736(98)07019-6

    Article  Google Scholar 

  4. Y Ohkubo H Kishikawa E Araki T Miyata S Isami S Motoyoshi et al. (1995) ArticleTitleIntensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study Diabetes Res Clin Pract 28 103–17 Occurrence Handle7587918 Occurrence Handle1:CAS:528:DyaK2MXpsVWgtrs%3D Occurrence Handle10.1016/0168-8227(95)01064-K

    Article  PubMed  CAS  Google Scholar 

  5. AM Shapiro JR Lakey EA Ryan GS Korbutt E Toth GL Warnock et al. (2000) ArticleTitleIslet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen N Engl J Med 343 230–8 Occurrence Handle10911004 Occurrence Handle1:CAS:528:DC%2BD3cXlvVSmt7k%3D Occurrence Handle10.1056/NEJM200007273430401

    Article  PubMed  CAS  Google Scholar 

  6. S Matsumoto T Okitsu Y Iwanaga H Noguchi H Nagata Y Yonekawa et al. (2005) ArticleTitleInsulin independence after living-donor distal pancreatectomy and islet allotransplantation Lancet 365 1642–4 Occurrence Handle15889479 Occurrence Handle1:CAS:528:DC%2BD2MXktVGku70%3D Occurrence Handle10.1016/S0140-6736(05)66383-0

    Article  PubMed  CAS  Google Scholar 

  7. Matsumoto S, Okitsu T, Iwanaga Y, Noguchi H, Nagata H, Yonekawa Y, et al. Successful islet transplantation from non-heart-beating donor pancreata using modified Ricordi islet isolation method. Transplantation 2005; in press

  8. CG Perry JR Petrie (2002) ArticleTitleInsulin-sensitising agents: beyond thiazolidinediones Expert Opin Emerg Drugs 7 165–74 Occurrence Handle15989542 Occurrence Handle1:CAS:528:DC%2BD38XltlOks7k%3D Occurrence Handle10.1517/14728214.7.1.165

    Article  PubMed  CAS  Google Scholar 

  9. H Noguchi H Kaneto GC Weir S Bonner-Weir (2003) ArticleTitlePDX-1 protein containing its own antennapedia-like protein transduction domain can transduce pancreatic duct and islet cells Diabetes 52 1732–7 Occurrence Handle12829640 Occurrence Handle1:CAS:528:DC%2BD3sXltlWhtb8%3D

    PubMed  CAS  Google Scholar 

  10. H Noguchi M Matsushita S Matsumoto YF Lu H Matsui S Bonner-Weir (2005) ArticleTitleMechanism of PDX-1 protein transduction Biochem Biophys Res Commun 332 68–74 Occurrence Handle15896300 Occurrence Handle1:CAS:528:DC%2BD2MXkt1OjtLc%3D Occurrence Handle10.1016/j.bbrc.2005.04.092

    Article  PubMed  CAS  Google Scholar 

  11. Noguchi H, Matsumoto S, Okitsu T, Iwanaga Y, Yonekawa Y, Nagata H, et al. PDX-1 protein is internalized by lipid raft-dependent macropinocytosis. Cell Transplant 2005; in press

  12. A Prochiantz (2000) ArticleTitleMessenger proteins: homeoproteins, TAT and others Curr Opin Cell Biol 12 400–6 Occurrence Handle10873818 Occurrence Handle1:CAS:528:DC%2BD3cXlt1Srtbw%3D Occurrence Handle10.1016/S0955-0674(00)00108-3

    Article  PubMed  CAS  Google Scholar 

  13. A Joliot A Prochiantz (2004) ArticleTitleTransduction peptides: from technology to physiology Nat Cell Biol 6 189–96 Occurrence Handle15039791 Occurrence Handle1:CAS:528:DC%2BD2cXhs1Ggt7g%3D Occurrence Handle10.1038/ncb0304-189

    Article  PubMed  CAS  Google Scholar 

  14. M Matsushita H Noguchi YF Lu K Tomizawa H Michiue ST Li et al. (2004) ArticleTitlePhoto-acceleration of protein release from endosome in the protein transduction system FEBS Lett 572 221–6 Occurrence Handle15304352 Occurrence Handle1:CAS:528:DC%2BD2cXmsVGhtrk%3D Occurrence Handle10.1016/j.febslet.2004.07.033

    Article  PubMed  CAS  Google Scholar 

  15. G Elliott P O'Hare (1997) ArticleTitleIntercellular trafficking and protein delivery by a herpesvirus structural protein Cell 88 223–33 Occurrence Handle9008163 Occurrence Handle1:CAS:528:DyaK2sXpsV2lsA%3D%3D Occurrence Handle10.1016/S0092-8674(00)81843-7

    Article  PubMed  CAS  Google Scholar 

  16. SR Schwarze A Ho A Vocero-Akbani SF Dowdy (1999) ArticleTitleIn vivo protein transduction: delivery of a biologically active protein into the mouse Science 285 1569–72 Occurrence Handle10477521 Occurrence Handle1:CAS:528:DyaK1MXlslOru78%3D Occurrence Handle10.1126/science.285.5433.1569

    Article  PubMed  CAS  Google Scholar 

  17. T Watanabe N Shibata KA Westerman T Okitsu JE Allain M Sakaguchi et al. (2003) ArticleTitleEstablishment of immortalized human hepatic stellate scavenger cells to develop bioartificial livers Transplantation 75 1873–80 Occurrence Handle12811248 Occurrence Handle1:CAS:528:DC%2BD3sXks1yqurs%3D Occurrence Handle10.1097/01.TP.0000064621.50907.A6

    Article  PubMed  CAS  Google Scholar 

  18. T Matsumura M Takesue KA Westerman T Okitsu M Sakaguchi T Fukazawa et al. (2004) ArticleTitleEstablishment of an immortalized human-liver endothelial cell line with SV40T and hTERT Transplantation 77 1357–65 Occurrence Handle15167590 Occurrence Handle1:CAS:528:DC%2BD2cXlvVSitrg%3D Occurrence Handle10.1097/01.TP.0000124286.82961.7E

    Article  PubMed  CAS  Google Scholar 

  19. C Bonny A Oberson S Negri C Sauser DF Schorderet (2001) ArticleTitleCell-permeable peptide inhibitors of JNK: novel blockers of beta-cell death Diabetes 50 77–82 Occurrence Handle11147798 Occurrence Handle1:CAS:528:DC%2BD3MXis1Ontw%3D%3D

    PubMed  CAS  Google Scholar 

  20. H Kaneto Y Nakatani T Miyatsuka D Kawamori TA Matsuoka M Matsuhisa et al. (2004) ArticleTitlePossible novel therapy for diabetes with cell-permeable JNK-inhibitory peptide Nat Med 10 1128–32 Occurrence Handle15448687 Occurrence Handle1:CAS:528:DC%2BD2cXnvFyntbg%3D Occurrence Handle10.1038/nm1111

    Article  PubMed  CAS  Google Scholar 

  21. J Embury D Klein A Pileggi M Ribeiro S Jayaraman RD Molano et al. (2001) ArticleTitleProteins linked to a protein transduction domain efficiently transduce pancreatic islets Diabetes 50 1706–13 Occurrence Handle11473028 Occurrence Handle1:CAS:528:DC%2BD3MXlslKnur8%3D

    PubMed  CAS  Google Scholar 

  22. H Noguchi M Matsushita T Okitsu A Moriwaki K Tomizawa S Kang et al. (2004) ArticleTitleA new cell-permeable peptide allows successful allogeneic islet transplantation in mice Nat Med 10 305–9 Occurrence Handle14770176 Occurrence Handle1:CAS:528:DC%2BD2cXhs1Wnuro%3D Occurrence Handle10.1038/nm994

    Article  PubMed  CAS  Google Scholar 

  23. H Noguchi Y Nakai S Matsumoto M Kawaguchi M Ueda T Okitsu et al. (2005) ArticleTitleCell permeable peptide of JNK inhibitor prevents islet apoptosis immediately after isolation and improves islet graft function Am J Transplant 5 1848–55 Occurrence Handle15996231 Occurrence Handle1:CAS:528:DC%2BD2MXpsVaru7s%3D Occurrence Handle10.1111/j.1600-6143.2005.00985.x

    Article  PubMed  CAS  Google Scholar 

  24. M Matsushita K Tomizawa A Moriwaki ST Li H Terada H Matsui (2001) ArticleTitleA high-efficiency protein transduction system demonstrating the role of PKA in long-lasting long-term potentiation J Neurosci 21 6000–7 Occurrence Handle11487623 Occurrence Handle1:CAS:528:DC%2BD3MXlvFKmsL4%3D

    PubMed  CAS  Google Scholar 

  25. JC Mai H Shen SC Watkins T Cheng PD Robbins (2002) ArticleTitleEfficiency of protein transduction is cell type-dependent and is enhanced by dextran sulfate J Biol Chem 277 30208–18 Occurrence Handle12034749 Occurrence Handle1:CAS:528:DC%2BD38XmsVKhsbY%3D Occurrence Handle10.1074/jbc.M204202200

    Article  PubMed  CAS  Google Scholar 

  26. S Futaki T Suzuki W Ohashi T Yagami S Tanaka K Ueda et al. (2001) ArticleTitleArginine-rich peptides. An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery J Biol Chem 276 5836–40 Occurrence Handle11084031 Occurrence Handle1:CAS:528:DC%2BD3MXhs1KmtL0%3D Occurrence Handle10.1074/jbc.M007540200

    Article  PubMed  CAS  Google Scholar 

  27. MC Morris P Vidal L Chaloin F Heitz G Divita (1997) ArticleTitleA new peptide vector for efficient delivery of oligonucleotides into mammalian cells Nucleic Acids Res 25 2730–6 Occurrence Handle9207018 Occurrence Handle1:CAS:528:DyaK2sXks1GksL0%3D Occurrence Handle10.1093/nar/25.14.2730

    Article  PubMed  CAS  Google Scholar 

  28. M Pooga U Soomets M Hallbrink A Valkna K Saar K Rezaei et al. (1998) ArticleTitleCell penetrating PNA constructs regulate galanin receptor levels and modify pain transmission in vivo Nat Biotechnol 16 857–61 Occurrence Handle9743120 Occurrence Handle1:CAS:528:DyaK1cXlvFWktbw%3D Occurrence Handle10.1038/nbt0998-857

    Article  PubMed  CAS  Google Scholar 

  29. CG Ostenson AC Sandberg-Nordqvist J Chen M Hallbrink D Rotin U Langel et al. (2002) ArticleTitleOverexpression of protein-tyrosine phosphatase PTP sigma is linked to impaired glucose-induced insulin secretion in hereditary diabetic Goto-Kakizaki rats Biochem Biophys Res Commun 291 945–50 Occurrence Handle11866457 Occurrence Handle10.1006/bbrc.2002.6536 Occurrence Handle1:CAS:528:DC%2BD38XhsFWjsLY%3D

    Article  PubMed  CAS  Google Scholar 

  30. F Simeoni MC Morris F Heitz G Divita (2003) ArticleTitleInsight into the mechanism of the peptide-based gene delivery system MPG: implications for delivery of siRNA into mammalian cells Nucleic Acids Res 31 2717–24 Occurrence Handle12771197 Occurrence Handle1:CAS:528:DC%2BD3sXkt1Wqs7o%3D Occurrence Handle10.1093/nar/gkg385

    Article  PubMed  CAS  Google Scholar 

  31. M Lewin N Carlesso CH Tung XW Tang D Cory DT Scadden et al. (2000) ArticleTitleTat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells Nat Biotechnol 18 410–4 Occurrence Handle10748521 Occurrence Handle1:CAS:528:DC%2BD3cXis1Gmt7s%3D Occurrence Handle10.1038/74464

    Article  PubMed  CAS  Google Scholar 

  32. VP Torchilin R Rammohan V Weissig TS Levchenko (2001) ArticleTitleTAT peptide on the surface of liposomes affords their efficient intracellular delivery even at low temperature and in the presence of metabolic inhibitors Proc Natl Acad Sci USA 98 8786–91 Occurrence Handle11438707 Occurrence Handle1:CAS:528:DC%2BD3MXls1Witbg%3D Occurrence Handle10.1073/pnas.151247498

    Article  PubMed  CAS  Google Scholar 

  33. M Sakaguchi T Nukui H Sonegawa H Murata J Futami H Yamada et al. (2005) ArticleTitleTargeted disruption of transcriptional regulatory function of p53 by a novel efficient method for introducing a decoy oligonucleotide into nuclei Nucleic Acids Res 33 e88 Occurrence Handle15920103 Occurrence Handle10.1093/nar/gni088 Occurrence Handle1:CAS:528:DC%2BD2MXkvVSgtr4%3D

    Article  PubMed  CAS  Google Scholar 

  34. S Futaki W Ohashi T Suzuki M Niwa S Tanaka K Ueda et al. (2001) ArticleTitleStearylated arginine-rich peptides: a new class of transfection systems Bioconjug Chem 12 1005–11 Occurrence Handle11716693 Occurrence Handle1:CAS:528:DC%2BD3MXnvVWmtrk%3D Occurrence Handle10.1021/bc015508l

    Article  PubMed  CAS  Google Scholar 

  35. JP Richard K Melikov E Vives C Ramos B Verbeure MJ Gait et al. (2003) ArticleTitleCell-penetrating peptides. A reevaluation of the mechanism of cellular uptake J Biol Chem 278 585–90 Occurrence Handle12411431 Occurrence Handle1:CAS:528:DC%2BD38XpvVWnsrk%3D Occurrence Handle10.1074/jbc.M209548200

    Article  PubMed  CAS  Google Scholar 

  36. G Drin S Cottin E Blanc AR Rees J Temsamani (2003) ArticleTitleStudies on the internalization mechanism of cationic ell-penetrating peptides J Biol Chem 278 31192–201 Occurrence Handle12783857 Occurrence Handle1:CAS:528:DC%2BD3sXmtFequrw%3D Occurrence Handle10.1074/jbc.M303938200

    Article  PubMed  CAS  Google Scholar 

  37. H Noguchi S Bonner-Weir FY Wei M Matsushita S Matsumoto (2005) ArticleTitleBETA2/NeuroD protein can be transduced into cells due to an arginine- and lysine-rich sequence Diabetes 54 2859–66 Occurrence Handle16186386 Occurrence Handle1:CAS:528:DC%2BD2MXhtV2rs77J

    PubMed  CAS  Google Scholar 

  38. JS Wadia RV Stan SF Dowdy (2004) ArticleTitleTransducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis Nat Med 10 310–5 Occurrence Handle14770178 Occurrence Handle1:CAS:528:DC%2BD2cXhs1Wnurg%3D Occurrence Handle10.1038/nm996

    Article  PubMed  CAS  Google Scholar 

  39. R Fischer K Kohler M Fotin-Mleczek R Brock (2004) ArticleTitleA stepwise dissection of the intracellular fate of cationic cell-penetrating peptides J Biol Chem 279 12625–35 Occurrence Handle14707144 Occurrence Handle1:CAS:528:DC%2BD2cXitl2gtrs%3D Occurrence Handle10.1074/jbc.M311461200

    Article  PubMed  CAS  Google Scholar 

  40. K Sandvig B van Deurs (2000) ArticleTitleEntry of ricin and Shiga toxin into cells: molecular mechanisms and medical perspectives EMBO J 19 5943–50 Occurrence Handle11080141 Occurrence Handle1:CAS:528:DC%2BD3cXovVaisLs%3D Occurrence Handle10.1093/emboj/19.22.5943

    Article  PubMed  CAS  Google Scholar 

  41. JM Lord LM Roberts (1998) ArticleTitleToxin entry: retrograde transport through the secretory pathway J Cell Biol 140 733–6 Occurrence Handle9472027 Occurrence Handle1:CAS:528:DyaK1cXhtlegt7k%3D Occurrence Handle10.1083/jcb.140.4.733

    Article  PubMed  CAS  Google Scholar 

  42. S Matsumoto K Tanaka (2005) ArticleTitlePancreatic islet cell transplantation using non-heart-beating donors (NHBDs) J Hepatobiliary Pancreat Surg 12 227–30 Occurrence Handle15995811 Occurrence Handle10.1007/s00534-005-0978-z

    Article  PubMed  Google Scholar 

  43. S Matsumoto SA Qualley S Goel DK Hagman IR Sweet V Poitout et al. (2002) ArticleTitleEffect of the two-layer (University of Wisconsin solution-perfluorochemical plus O2) method of pancreas preservation on human islet isolation, as assessed by the Edmonton Isolation Protocol Transplantation 74 1414–9 Occurrence Handle12451242 Occurrence Handle1:CAS:528:DC%2BD38XptVSiurg%3D Occurrence Handle10.1097/00007890-200211270-00013

    Article  PubMed  CAS  Google Scholar 

  44. S Matsumoto TH Rigley JA Reems Y Kuroda RB Stevens (2003) ArticleTitleImproved islet yields from Macaca nemestrina and marginal human pancreata after two-layer method preservation and endogenous trypsin inhibition Am J Transplant 3 53–63 Occurrence Handle12492711 Occurrence Handle1:CAS:528:DC%2BD3sXotFCisw%3D%3D Occurrence Handle10.1034/j.1600-6143.2003.30110.x

    Article  PubMed  CAS  Google Scholar 

  45. S Matsumoto Y Kuroda (2002) ArticleTitlePerfluorocarbon for organ preservation before transplantation Transplantation 74 1804–9 Occurrence Handle12499904 Occurrence Handle1:CAS:528:DC%2BD38Xpslaku7c%3D Occurrence Handle10.1097/00007890-200212270-00030

    Article  PubMed  CAS  Google Scholar 

  46. T Matsuda Y Suzuki Y Tanioka H Toyama K Kakinoki K Hiraoka et al. (2003) ArticleTitlePancreas preservation by the 2-layer cold storage method before islet isolation protects isolated islets against apoptosis through the mitochondrial pathway Surgery 134 437–45 Occurrence Handle14555931 Occurrence Handle10.1067/S0039-6060(03)00165-X

    Article  PubMed  Google Scholar 

  47. KK Rehman S Bertera R Bottino AN Balamurugan JC Mai Z Mi et al. (2003) ArticleTitleProtection of islets by in situ peptide-mediated transduction of the Ikappa B kinase inhibitor Nemo-binding domain peptide J Biol Chem 278 9862–8 Occurrence Handle12524423 Occurrence Handle1:CAS:528:DC%2BD3sXhvV2hsbw%3D Occurrence Handle10.1074/jbc.M207700200

    Article  PubMed  CAS  Google Scholar 

  48. MM Ribeiro D Klein A Pileggi RD Molano C Fraker C Ricordi et al. (2003) ArticleTitleHeme oxygenase-1 fused to a TAT peptide transduces and protects pancreatic beta-cells Biochem Biophys Res Commun 305 876–81 Occurrence Handle12767912 Occurrence Handle1:CAS:528:DC%2BD3sXktFGju78%3D Occurrence Handle10.1016/S0006-291X(03)00856-8

    Article  PubMed  CAS  Google Scholar 

  49. D Klein MM Ribeiro V Mendoza S Jayaraman NS Kenyon A Pileggi et al. (2004) ArticleTitleDelivery of Bcl-XL or its BH4 domain by protein transduciton inhibits apoptosis in human islets Biochem Biophys Res Commun 323 473–8 Occurrence Handle15369775 Occurrence Handle1:CAS:528:DC%2BD2cXnsVyqtrg%3D Occurrence Handle10.1016/j.bbrc.2004.08.116

    Article  PubMed  CAS  Google Scholar 

  50. J Aramburu MB Yaffe C Lopez-Rodriguez LC Cantley PG Hogan A Rao (1999) ArticleTitleAffinity-driven peptide selection of an NFAT inhibitor more selective than cyclosporin A Science 285 2129–33 Occurrence Handle10497131 Occurrence Handle1:CAS:528:DyaK1MXmt12jtLY%3D Occurrence Handle10.1126/science.285.5436.2129

    Article  PubMed  CAS  Google Scholar 

  51. M Hibi A Lin T Smeal A Minden M Karin (1993) ArticleTitleIdentification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain Genes Dev 7 2135–48 Occurrence Handle8224842 Occurrence Handle1:CAS:528:DyaK2cXisVyksQ%3D%3D

    PubMed  CAS  Google Scholar 

  52. B Derijard M Hibi IH Wu T Barrett B Su T Deng et al. (1994) ArticleTitleJNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain Cell 76 1025–37 Occurrence Handle8137421 Occurrence Handle1:CAS:528:DyaK2cXjtFygt78%3D Occurrence Handle10.1016/0092-8674(94)90380-8

    Article  PubMed  CAS  Google Scholar 

  53. RJ Davis (2000) ArticleTitleSignal transduction by the JNK group of MAP kinases Cell 103 239–52 Occurrence Handle11057897 Occurrence Handle1:CAS:528:DC%2BD3cXns1Cltrk%3D Occurrence Handle10.1016/S0092-8674(00)00116-1

    Article  PubMed  CAS  Google Scholar 

  54. L Chang M Karin (2001) ArticleTitleMammalian MAP kinase signaling cascades Nature 410 37–40 Occurrence Handle11242034 Occurrence Handle1:CAS:528:DC%2BD3MXhvVSgs7k%3D Occurrence Handle10.1038/35065000

    Article  PubMed  CAS  Google Scholar 

  55. J Hirosumi G Tuncman L Chang CZ Gorgun KT Uysal K Maeda et al. (2002) ArticleTitleA central role for JNK in obesity and insulin resistance Nature 420 333–6 Occurrence Handle12447443 Occurrence Handle1:CAS:528:DC%2BD38XovVekt7g%3D Occurrence Handle10.1038/nature01137

    Article  PubMed  CAS  Google Scholar 

  56. V Aguirre T Uchida L Yenush R Davis MF White (2000) ArticleTitleThe c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307) J Biol Chem 275 9047–54 Occurrence Handle10722755 Occurrence Handle1:CAS:528:DC%2BD3cXit1emt7Y%3D Occurrence Handle10.1074/jbc.275.12.9047

    Article  PubMed  CAS  Google Scholar 

  57. AM Manning RJ Davis (2003) ArticleTitleTargeting JNK for therapeutic benefit: from junk to gold? Nat Rev Drug Discov 2 554–65 Occurrence Handle12815381 Occurrence Handle1:CAS:528:DC%2BD3sXks1Oru7c%3D Occurrence Handle10.1038/nrd1132

    Article  PubMed  CAS  Google Scholar 

  58. H Kaneto G Xu N Fujii S Kim S Bonner-Weir GC Weir (2002) ArticleTitleInvolvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression J Biol Chem 277 30010–8 Occurrence Handle12011047 Occurrence Handle1:CAS:528:DC%2BD38XmsVKhs7o%3D Occurrence Handle10.1074/jbc.M202066200

    Article  PubMed  CAS  Google Scholar 

  59. D Kawamori Y Kajimoto H Kaneto Y Umayahara Y Fujitani T Miyatsuka et al. (2003) ArticleTitleOxidative stress induces nucleo-cytoplasmic translocation of pancreatic transcription factor PDX-1 through activation of c-Jun NH(2)-terminal kinase Diabetes 52 2896–904 Occurrence Handle14633849 Occurrence Handle1:CAS:528:DC%2BD3sXpsFagsLg%3D

    PubMed  CAS  Google Scholar 

  60. JA Corbett JL Wang MA Sweetland JR Lancaster SuffixJr ML McDaniel (1992) ArticleTitleInterleukin 1 beta induces the formation of nitric oxide by beta-cells purified from rodent islets of Langerhans. Evidence for the beta-cell as a source and site of action of nitric oxide J Clin Invest 90 2384–91 Occurrence Handle1334975 Occurrence Handle1:CAS:528:DyaK3sXnvFSrtw%3D%3D Occurrence Handle10.1172/JCI116129

    Article  PubMed  CAS  Google Scholar 

  61. H Kaneto J Fujii HG Seo K Suzuki T Matsuoka M Nakamura et al. (1995) ArticleTitleApoptotic cell death triggered by nitric oxide in pancreatic beta-cells Diabetes 44 733–8 Occurrence Handle7540572 Occurrence Handle1:CAS:528:DyaK2MXms1Cnu7g%3D

    PubMed  CAS  Google Scholar 

  62. A Ammendrup A Maillard K Nielsen N Aabenhus Andersen P Serup O Dragsbaek Madsen et al. (2000) ArticleTitleThe c-Jun amino-terminal kinase pathway is preferentially activated by interleukin-1 and controls apoptosis in differentiating pancreatic beta-cells Diabetes 49 1468–76 Occurrence Handle10969830 Occurrence Handle1:CAS:528:DC%2BD3cXmsVOrsLk%3D

    PubMed  CAS  Google Scholar 

  63. C Bonny A Oberson M Steinmann DF Schorderet P Nicod G Waeber (2000) ArticleTitleIB1 reduces cytokine-induced apoptosis of insulin-secreting cells J Biol Chem 275 16466–72 Occurrence Handle10748095 Occurrence Handle1:CAS:528:DC%2BD3cXjvFCntL4%3D Occurrence Handle10.1074/jbc.M908297199

    Article  PubMed  CAS  Google Scholar 

  64. T Mandrup-Poulsen (2001) ArticleTitlebeta-cell apoptosis: stimuli and signaling Diabetes 50 IssueIDSuppl 1 S58–63 Occurrence Handle11272204 Occurrence Handle1:CAS:528:DC%2BD3MXhtVOgtrY%3D

    PubMed  CAS  Google Scholar 

  65. G Waeber J Delplanque C Bonny V Mooser M Steinmann C Widmann et al. (2000) ArticleTitleThe gene MAPK8IP1, encoding islet-brain-1, is a candidate for type 2 diabetes Nat Genet 24 291–5 Occurrence Handle10700186 Occurrence Handle1:CAS:528:DC%2BD3cXhvFaqt7Y%3D Occurrence Handle10.1038/73523

    Article  PubMed  CAS  Google Scholar 

  66. J Dominguez-Bendala D Klein M Ribeiro C Ricordi L Inverardi R Pastori et al. (2005) ArticleTitleTAT-mediated neurogenin 3 protein transduction stimulates pancreatic endocrine differentiation in vitro Diabetes 54 720–6 Occurrence Handle15734848 Occurrence Handle1:CAS:528:DC%2BD2MXitlegs74%3D

    PubMed  CAS  Google Scholar 

  67. K Kilk M Magzoub M Pooga LE Eriksson U Langel A Graslund (2001) ArticleTitleCellular internalization of a cargo complex with a novel peptide derived from the third helix of the islet-1 homeodomain. Comparison with the penetratin peptide Bioconjug Chem 12 911–6 Occurrence Handle11716681 Occurrence Handle1:CAS:528:DC%2BD3MXnvFGmtro%3D Occurrence Handle10.1021/bc0100298

    Article  PubMed  CAS  Google Scholar 

  68. B Ensoli L Buonaguro G Barillari V Fiorelli R Gendelman RA Morgan et al. (1993) ArticleTitleRelease, uptake, and effects of extracellular human immunodeficiency virus type 1 Tat protein on cell growth and viral transactivation J Virol 67 277–87 Occurrence Handle8416373 Occurrence Handle1:CAS:528:DyaK3sXlsl2qtg%3D%3D

    PubMed  CAS  Google Scholar 

  69. A Joliot A Maizel D Rosenberg A Trembleau S Dupas M Volovitch et al. (1998) ArticleTitleIdentification of a signal sequence necessary for the unconventional secretion of Engrailed homeoprotein Curr Biol 8 856–63 Occurrence Handle9705930 Occurrence Handle1:CAS:528:DyaK1cXks1Ghtbc%3D Occurrence Handle10.1016/S0960-9822(07)00346-6

    Article  PubMed  CAS  Google Scholar 

  70. A Prochiantz A Joliot (2003) ArticleTitleCan transcription factors function as cell-cell signaling molecules? Nat Rev Mol Cell Biol 4 814–9 Occurrence Handle14570063 Occurrence Handle1:CAS:528:DC%2BD3sXovFOlsr4%3D

    PubMed  CAS  Google Scholar 

  71. FJ Naya HP Huang Y Qiu H Mutoh FJ DeMayo AB Leiter et al. (1997) ArticleTitleDiabetes, defective pancreatic morphogenesis, and abnormal enteroendocrine differentiation in BETA2/neuroD-deficient mice Genes Dev 11 2323–34 Occurrence Handle9308961 Occurrence Handle1:CAS:528:DyaK2sXmtl2hu7k%3D

    PubMed  CAS  Google Scholar 

  72. J Jonsson L Carlsson T Edlund H Edlund (1994) ArticleTitleInsulin-promoter-factor 1 is required for pancreas development in mice Nature 371 606–9 Occurrence Handle7935793 Occurrence Handle1:CAS:528:DyaK2cXmsFahsbg%3D Occurrence Handle10.1038/371606a0

    Article  PubMed  CAS  Google Scholar 

  73. S Marshak E Benshushan M Shoshkes L Havin E Cerasi D Melloul (2000) ArticleTitleFunctional conservation of regulatory elements in the pdx-1 gene: PDX-1 and hepatocyte nuclear factor 3beta transcription factors mediate beta-cell-specific expression Mol Cell Biol 20 7583–90 Occurrence Handle11003654 Occurrence Handle1:CAS:528:DC%2BD3cXnt1ait7w%3D Occurrence Handle10.1128/MCB.20.20.7583-7590.2000

    Article  PubMed  CAS  Google Scholar 

  74. T Miyachi H Maruyama T Kitamura S Nakamura H Kawakami (1999) ArticleTitleStructure and regulation of the human NeuroD (BETA2/BHF1) gene Brain Res Mol Brain Res 69 223–31 Occurrence Handle10366743 Occurrence Handle1:CAS:528:DyaK1MXjsVShu7Y%3D Occurrence Handle10.1016/S0169-328X(99)00112-6

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

About this article

Cite this article

Noguchi, H., Matsumoto, S. Protein transduction technology offers a novel therapeutic approach for diabetes. J Hepatobiliary Pancreat Surg 13, 306–313 (2006). https://doi.org/10.1007/s00534-005-1038-4

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00534-005-1038-4

Key words

Navigation