Anti-inflammatory properties of exenatide in human pancreatic islets

Cell Transplantation

Volumn 21, Issue 4, 2012, Pages 633-648

  Cechin, S R ^a   Perez Alvarez I ^a   Fenjves, E ^a   Molano, R D ^a   Pileggi, A ^a   Berggren, P O ^a,b   Ricordi, C ^a,b   Pastori, R L ^a  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^b KAROLINSKA INSTITUTE   (Sweden)

Author keywords

Cytokines; Exenatide; Glucagon like peptide 1; Human pancreatic islets; Inflammation; Islet transplantation; Nude mice; Proteinase inhibitor 9 (PI 9)

Indexed keywords

CASPASE 3; EXENDIN 4; GAMMA INTERFERON; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; INTERLEUKIN 1BETA; INTERLEUKIN 2; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PROTEIN KINASE B; PROTEINASE INHIBITOR 9; SERINE PROTEINASE INHIBITOR; STAT3 PROTEIN; THROMBOPLASTIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CELL PROTECTION; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; IMMUNOREGULATION; IN VITRO STUDY; MOUSE; NONHUMAN; PANCREAS ISLET; PANCREAS ISLET ALPHA CELL; PANCREAS ISLET BETA CELL; PANCREAS ISLET TRANSPLANTATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN INDUCTION; PROTEIN LOCALIZATION;

MUS; MUS MUSCULUS;

EID: 84930476726     PISSN: 09636897     EISSN: None     Source Type: Journal    
DOI: 10.3727/096368911X576027     Document Type: Article

References (68)

1. Abdelli, S.; Ansite, J.; Roduit, R.; Borsello, T.; Matsumoto, I.; Sawada, T.; Allaman-Pillet, N.; Henry, H.; Beckmann, J.; Hering, B.; Bonny, C. Intracellular stress signaling pathways activated during human islet preparation and following acute cytokine exposure. Diabetes 53(11):2815-2823; 2004.
2. Aikin, R.; Maysinger, D.; Rosenberg, L. Cross-talk between phosphatidylinositol 3-kinase/AKT and c-jun NH2-terminal kinase mediates survival of isolated human islets. Endocrinology 145(10):4522-4531; 2004.
3. Anderson, S. L.; Trujillo, J. M. Association of pancreatitis with glucagon-like peptide-1 agonist use. Ann. Pharmacother. 44(5):904-909; 2010.
4. Ayoub, W. A.; Kumar, A. A.; Naguib, H. S.; Taylor, H. C. Exenatide-induced acute pancreatitis. Endocr. Pract. 16(1):80-83; 2010.
5. Bennet, W.; Groth, C.; Larsson, R.; Nilsson, B.; Korsgren, O. Isolated human islets trigger an instant blood mediated inflammatory reaction: Implications for intraportal islet transplantation as a treatment for patients with type 1 diabetes. Ups. J. Med. Sci. 105(2):125-133; 2000.
6. Berman, D. M.; Cabrera, O.; Kenyon, N. M.; Miller, J.; Tam, S. H.; Khandekar, V. S.; Picha, K. M.; Soderman, A. R.; Jordan, R. E.; Bugelski, P. J.; Horninger, D.; Lark, M.; Davis, J. E.; Alejandro, R.; Berggren, P. O.; Zimmerman, M.; O'Neil, J. J.; Ricordi, C.; Kenyon, N. S. Interference with tissue factor prolongs intrahepatic islet allograft survival in a nonhuman primate marginal mass model. Transplantation 84(3):308-315; 2007.
7. Bladergroen, B.; Meijer, C.; ten Berge, R.; Hack, C.; Muris, J.; Dukers, D.; Chott, A.; Kazama, Y.; Oudejans, J.; van Berkum, O.; Kummer, J. Expression of the gran-zyme B inhibitor, protease inhibitor 9, by tumor cells in patients with non-Hodgkin and Hodgkin lymphoma: A novel protective mechanism for tumor cells to circumvent the immune system? Blood 99(1):232-237; 2002.
8. Bladergroen, B. A.; Strik, M. C.; Bovenschen, N.; van Berkum, O.; Scheffer, G. L.; Meijer, C. J.; Hack, C. E.; Kummer, J. A. The granzyme B inhibitor, protease inhibitor 9, is mainly expressed by dendritic cells and at immune-privileged sites. J. Immunol. 166(5):3218-3225; 2001.
9. Blandino-Rosano, M.; Perez-Arana, G.; Mellado-Gil, J.; Segundo, C.; Aguilar-Diosdado, M. Anti-proliferative effect of pro-inflammatory cytokines in cultured beta cells is associated with extracellular signal-regulated kinase 1/2 pathway inhibition: Protective role of glucagon-like peptide-1. J. Mol. Endocrinol. 41(1):35-44; 2008.
10. Blonde, L.; Klein, E.; Han, J.; Zhang, B.; Mac, S.; Poon, T.; Taylor, K.; Trautmann, M.; Kim, D.; Kendall, D. Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes. Metab. 8(4):436-447; 2006.
11. Bonny, C.; Oberson, A.; Negri, S.; Sauser, C.; Schorderet, D. Cell-permeable peptide inhibitors of JNK: Novel blockers of beta-cell death. Diabetes 50(1):77-82; 2001.
12. Bottino, R.; Balamurugan, A. N.; Tse, H.; Thirunavukkarasu, C.; Ge, X.; Profozich, J.; Milton, M.; Ziegenfuss, A.; Trucco, M.; Piganelli, J. D. Response of human islets to isolation stress and the effect of antioxidant treatment. Diabetes 53(10):2559-2568; 2004.
13. Cabrera, O.; Jacques-Silva, M. C.; Berman, D. M.; Fachado, A.; Echeverri, F.; Poo, R.; Khan, A.; Kenyon, N. S.; Ricordi, C.; Berggren, P. O.; Caicedo, A. Automated, high-throughput assays for evaluation of human pancreatic islet function. Cell Transplant. 16(10):1039-1048; 2007.
14. Calara, F.; Taylor, K.; Han, J.; Zabala, E.; Carr, E.; Wintle, M.; Fineman, M. A randomized, open-label, crossover study examining the effect of injection site on bioavailability of exenatide (synthetic exendin-4). Clin. Ther. 27(2):210-215; 2005.
15. Christen, U.; von Herrath, M. G. IP-10 and type 1 diabetes: A question of time and location. Autoimmunity 37(4): 273-282; 2004.
16. Cobianchi, L.; Fornoni, A.; Pileggi, A.; Molano, R.; Sanabria, N.; Gonzalez-Quintana, J.; Bocca, N.; Marzorati, S.; Zahr, E.; Hogan, A.; Ricordi, C.; Inverardi, L. Riboflavin inhibits IL-6 expression and p38 activation in islet cells. Cell Transplant. 17(5):559-566; 2008.
17. Copley, K.; McCowen, K.; Hiles, R.; Nielsen, L. L.; Young, A.; Parkes, D. G. Investigation of exenatide elimination and its in vivo and in vitro degradation. Curr. Drug. Metab. 7(4):367-374; 2006.
18. Cunningham, T.; Jiang, X.; Shapiro, D. Expression of high levels of human proteinase inhibitor 9 blocks both perforin/granzyme and Fas/Fas ligand-mediated cytotoxicity. Cell. Immunol. 245(1):32-41; 2007.
19. Cure, P.; Pileggi, A.; Alejandro, R. Exenatide and rare adverse events. N. Engl. J. Med. 358(18):1969-1972; 2008.
20. Deacon, C. Circulation and degradation of GIP and GLP- 1. Horm. Metab. Res. 36(11-12):761-765; 2004.
21. Donath, M. Y.; Storling, J.; Berchtold, L. A.; Billestrup, N.; Mandrup-Poulsen, T. Cytokines and beta-cell biology: From concept to clinical translation. Endocr. Rev. 29(3): 334-350; 2008.
22. Drucker, D. Enhancing incretin action for the treatment of type 2 diabetes. Diabetes Care 26(10):2929-2940; 2003.
23. Drucker, D.; Nauck, M. The incretin system: Glucagonlike peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368(9548):1696-1705; 2006.
24. Eizirik, D.; Sandler, S.; Welsh, N.; Cetkovic-Cvrlje, M.; Nieman, A.; Geller, D.; Pipeleers, D.; Bendtzen, K.; Hellerstrom, C. Cytokines suppress human islet function irrespective of their effects on nitric oxide generation. J. Clin. Invest. 93(5):1968-1974; 1994.
25. Ellingsgaard, H.; Ehses, J.; Hammar, E.; Van Lommel, L.; Quintens, R.; Martens, G.; Kerr-Conte, J.; Pattou, F.; Berney, T.; Pipeleers, D.; Halban, P.; Schuit, F.; Donath, M. Interleukin-6 regulates pancreatic alpha-cell mass expansion. Proc. Natl. Acad. Sci. USA 105(35):13163-13168; 2008.
26. Eng, J.; Kleinman, W.; Singh, L.; Singh, G.; Raufman, J. Isolation and characterization of exendin-4, an exendin-3analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J. Biol. Chem. 267(11):7402-7405; 1992.
27. Faradji, R. N.; Froud, T.; Messinger, S.; Monroy, K.; Pileggi, A.; Mineo, D.; Tharavanij, T.; Mendez, A. J.; Ricordi, C.; Alejandro, R. Long-term metabolic and hormonal effects of exenatide on islet transplant recipients with allograft dysfunction. Cell Transplant. 18(10):1247-1259; 2009.
28. Faradji, R. N.; Tharavanij, T.; Messinger, S.; Froud, T.; Pileggi, A.; Monroy, K.; Mineo, D.; Baidal, D. A.; Cure, P.; Ponte, G.; Mendez, A. J.; Selvaggi, G.; Ricordi, C.; Alejandro, R. Long-term insulin independence and improvement in insulin secretion after supplemental islet infusion under exenatide and etanercept. Transplantation 86(12):1658-1665; 2008.
29. Farilla, L.; Bulotta, A.; Hirshberg, B.; Li Calzi, S.; Khoury, N.; Noushmehr, H.; Bertolotto, C.; Di Mario, U.; Harlan, D.; Perfetti, R. Glucagon-like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets. Endocrinology 144(12): 5149-5158; 2003.
30. Ferdaoussi, M.; Abdelli, S.; Yang, J.; Cornu, M.; Niederhauser, G.; Favre, D.; Widmann, C.; Regazzi, R.; Thorens, B.; Waeber, G.; Abderrahmani, A. Exendin-4 protects beta-cells from interleukin-1 beta-induced apo-ptosis by interfering with the c-Jun NH2-terminal kinase pathway. Diabetes 57(5):1205-1215; 2008.
31. Fornoni, A.; Cobianchi, L.; Sanabria, N. Y.; Pileggi, A.; Molano, R. D.; Ichii, H.; Rosero, S.; Inverardi, L.; Ricordi, C.; Pastori, R. L. The l-isoform but not d-isoforms of a JNK inhibitory peptide protects pancreatic beta-cells. Biochem. Biophys. Res. Commun. 354(1):227-233; 2007.
32. Fornoni, A.; Pileggi, A.; Molano, R.; Sanabria, N.; Tejada, T.; Gonzalez-Quintana, J.; Ichii, H.; Inverardi, L.; Ricordi, C.; Pastori, R. Inhibition of c-jun N terminal kinase (JNK) improves functional beta cell mass in human islets and leads to AKT and glycogen synthase kinase-3 (GSK-3) phosphorylation. Diabetologia 51(2):298-308; 2008.
33. Froud, T.; Faradji, R. N.; Pileggi, A.; Messinger, S.; Baidal, D. A.; Ponte, G. M.; Cure, P. E.; Monroy, K.; Mendez, A.; Selvaggi, G.; Ricordi, C.; Alejandro, R. The use of exenatide in islet transplant recipients with chronic allograft dysfunction: Safety, efficacy, and metabolic effects. Transplantation 86(1):36-45; 2008.
34. Gangemi, A.; Salehi, P.; Hatipoglu, B.; Martellotto, J.; Barbaro, B.; Kuechle, J. B.; Qi, M.; Wang, Y.; Pallan, P.; Owens, C.; Bui, J.; West, D.; Kaplan, B.; Benedetti, E.; Oberholzer, J. Islet transplantation for brittle type 1 diabetes: The UIC protocol. Am. J. Transplant. 8(6):1250-1261; 2008.
35. Gedulin, B.; Nikoulina, S.; Smith, P.; Gedulin, G.; Nielsen, L.; Baron, A.; Parkes, D.; Young, A. Exenatide (exendin-4) improves insulin sensitivity and {beta}-cell mass in insulin-resistant obese fa/fa Zucker rats independent of glycemia and body weight. Endocrinology 146(4):2069-2076; 2005.
36. Ghofaili, K.; Fung, M.; Ao, Z.; Meloche, M.; Shapiro, R.; Warnock, G.; Elahi, D.; Meneilly, G.; Thompson, D. Effect of exenatide on beta cell function after islet transplantation in type 1 diabetes. Transplantation 83(1):24-28; 2007.
37. Goke, R.; Fehmann, H. C.; Linn, T.; Schmidt, H.; Krause, M.; Eng, J.; Goke, B. Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting beta-cells. J. Biol. Chem. 268(26):19650-19655; 1993.
38. Hohmeier, H.; Tran, V.; Chen, G.; Gasa, R.; Newgard, C. Inflammatory mechanisms in diabetes: Lessons from the beta-cell. Int. J. Obes. Relat. Metab. Disord. 27 (Suppl. 3):S12-16; 2003.
39. Hui, H.; Nourparvar, A.; Zhao, X.; Perfetti, R. Glucagonlike peptide-1 inhibits apoptosis of insulin-secreting cells via a cyclic 5'-adenosine monophosphate-dependent protein kinase A- and a phosphatidylinositol 3-kinase-dependent pathway. Endocrinology 144(4):1444-1455; 2003.
40. Ichii, H.; Miki, A.; Yamamoto, T.; Molano, R. D.; Barker, S.; Mita, A.; Rodriguez-Diaz, R.; Klein, D.; Pastori, R.; Alejandro, R.; Inverardi, L.; Pileggi, A.; Ricordi, C. Characterization of pancreatic ductal cells in human islet preparations. Lab. Invest. 88(11):1167-1177; 2008.
41. Ichii, H.; Sakuma, Y.; Pileggi, A.; Fraker, C.; Alvarez, A.; Montelongo, J.; Szust, J.; Khan, A.; Inverardi, L.; Naziruddin, B.; Levy, M. F.; Klintmalm, G. B.; Goss, J. A.; Alejandro, R.; Ricordi, C. Shipment of human islets for transplantation. Am. J. Transplant. 7(4):1010-1020; 2007.
42. Jiang, X.; Orr, B.; Kranz, D.; Shapiro, D. Estrogen induction of the granzyme B inhibitor, proteinase inhibitor 9, protects cells against apoptosis mediated by cytotoxic T lymphocytes and natural killer cells. Endocrinology 147(3):1419-1426; 2006.
43. Kang, J.; Chang, S.; Jang, H.; Kim, D.; Ryu, G.; Ko, S.; Jeong, I.; Jo, Y.; Kim, M. Exendin-4 inhibits interleukin-1beta-induced iNOS expression at the protein level, but not at the transcriptional and posttranscriptional levels, in RINm5F beta-cells. J. Endocrinol. 202(1):65-75; 2009.
44. Kannan-Thulasiraman, P.; Shapiro, D. Modulators of inflammation use nuclear factor-kappa B and activator protein-1 sites to induce the caspase-1 and granzyme B inhibitor, proteinase inhibitor 9. J. Biol. Chem. 277(43): 41230-41239; 2002.
45. Kawasaki, Y.; Harashima, S.; Sasaki, M.; Mukai, E.; Nakamura, Y.; Harada, N.; Toyoda, K.; Hamasaki, A.; Yamane, S.; Yamada, C.; Yamada, Y.; Seino, Y.; Inagaki, N. Exendin-4 protects pancreatic beta cells from the cytotoxic effect of rapamycin by inhibiting JNK and p38 phosphorylation. Horm. Metab. Res. 42(5):311-317.
46. Kim Chung le, T.; Hosaka, T.; Yoshida, M.; Harada, N.; Sakaue, H.; Sakai, T.; Nakaya, Y. Exendin-4, a GLP-1 receptor agonist, directly induces adiponectin expression through protein kinase A pathway and prevents inflammatory adipokine expression. Biochem. Biophys. Res. Commun. 390(3):613-618; 2009.
47. Kim, S.; Moon, M.; Park, S. Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson's disease. J. Endocrinol. 202(3):431-439; 2009.
48. Kin, T.; Senior, P.; O'Gorman, D.; Richer, B.; Salam, A.; Shapiro, A. M. Risk factors for islet loss during culture prior to transplantation. Transpl. Int. 21(11):1029-1035; 2008.
49. Livak, K.; Schmittgen, T. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4):402-408; 2001.
50. Moh, A.; Zhang, W.; Yu, S.; Wang, J.; Xu, X.; Li, J.; Fu, X. STAT3 sensitizes insulin signaling by negatively regulating glycogen synthase kinase-3 beta. Diabetes 57(5):1227-1235; 2008.
51. Nakano, M.; Matsumoto, I.; Sawada, T.; Ansite, J.; Oberbroeckling, J.; Zhang, H. J.; Kirchhof, N.; Shearer, J.; Sutherland, D. E.; Hering, B. J. Caspase-3 inhibitor prevents apoptosis of human islets immediately after isolation and improves islet graft function. Pancreas 29(2): 104-109; 2004.
52. Nauck, M.; Homberger, E.; Siegel, E.; Allen, R.; Eaton, R.; Ebert, R.; Creutzfeldt, W. Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J. Clin. Endocrinol. Metab. 63(2): 492-498; 1986.
53. Paraskevas, S.; Aikin, R.; Maysinger, D.; Lakey, J. R.; Cavanagh, T. J.; Agapitos, D.; Wang, R.; Rosenberg, L. Modulation of JNK and p38 stress activated protein kinases in isolated islets of Langerhans: Insulin as an autocrine survival signal. Ann. Surg. 233(1):124-133; 2001.
54. Paraskevas, S.; Aikin, R.; Maysinger, D.; Lakey, J. R.; Cavanagh, T. J.; Hering, B.; Wang, R.; Rosenberg, L. Activation and expression of ERK, JNK, and p38 MAP-kinases in isolated islets of Langerhans: Implications for cultured islet survival. FEBS Lett. 455(3):203-208; 1999.
55. Park, S.; Dong, X.; Fisher, T.; Dunn, S.; Omer, A.; Weir, G.; White, M. Exendin-4 uses Irs2 signaling to mediate pancreatic beta cell growth and function. J. Biol. Chem. 281(2):1159-1168; 2006.
56. Pileggi, A.; Molano, R. D.; Berney, T.; Ichii, H.; San Jose, S.; Zahr, E.; Poggioli, R.; Linetsky, E.; Ricordi, C.; Inverardi, L. Prolonged allogeneic islet graft survival by protoporphyrins. Cell Transplant. 14(2-3):85-96; 2005.
57. Pileggi, A.; Ribeiro, M. M.; Hogan, A. R.; Molano, R. D.; Cobianchi, L.; Ichii, H.; Embury, J.; Inverardi, L.; Fornoni, A.; Ricordi, C.; Pastori, R. L. Impact of pancreatic cold preservation on rat islet recovery and function. Transplantation 87(10):1442-1450; 2009.
58. Pugazhenthi, U.; Velmurugan, K.; Tran, A.; Mahaffey, G.; Pugazhenthi, S. Anti-inflammatory action of exendin-4 in human islets is enhanced by phosphodiesterase inhibitors: Potential therapeutic benefits in diabetic patients. Diabetologia 53(11):2357-2368; 2010.
59. Rezende, L.; Vieira, A.; Negro, A.; Langone, F.; Boschero, A. Ciliary neurotrophic factor (CNTF) signals through STAT3-SOCS3 pathway and protects rat pancreatic islets from cytokine-induced apoptosis. Cytokine 46(1):65-71; 2009.
60. Ricordi, C.; Lacy, P.; Finke, E.; Olack, B.; Scharp, D. Automated method for isolation of human pancreatic islets. Diabetes 37(4):413-420; 1988.
61. Ritzel, R.; Orskov, C.; Holst, J.; Nauck, M. Pharmacokinetic, insulinotropic, and glucagonostatic properties of GLP-1 [7-36 amide] after subcutaneous injection in healthy volunteers. Dose-response-relationships. Diabetologia 38(6): 720-725; 1995.
62. Rosenberg, L.; Wang, R.; Paraskevas, S.; Maysinger, D. Structural and functional changes resulting from islet isolation lead to islet cell death. Surgery 126(2):393-398; 1999.
63. Tews, D.; Lehr, S.; Hartwig, S.; Osmers, A.; Paslack, W.; Eckel, J. Anti-apoptotic action of exendin-4 in INS-1 beta cells: Comparative protein pattern analysis of isolated mitochondria. Horm. Metab. Res. 41(4):294-301; 2009.
64. Tews, D.; Werner, U.; Eckel, J. Enhanced protection against cytokine- and fatty acid-induced apoptosis in pancreatic beta cells by combined treatment with glucagonlike peptide-1 receptor agonists and insulin analogues. Horm. Metab. Res. 40(3):172-180; 2008.
65. Tornehave, D.; Kristensen, P.; Romer, J.; Knudsen, L. B.; Heller, R. S. Expression of the GLP-1 receptor in mouse, rat, and human pancreas. J. Histochem. Cytochem. 56(9): 841-851; 2008.
66. Wang, X.; Zhou, J.; Doyle, M.; Egan, J. Glucagon-like peptide-1 causes pancreatic duodenal homeobox-1 protein translocation from the cytoplasm to the nucleus of pancreatic beta-cells by a cyclic adenosine monophosphate/protein kinase A-dependent mechanism. Endocrinology 142(5): 1820-1827; 2001.
67. Xu, G.; Kaneto, H.; Lopez-Avalos, M.; Weir, G.; Bonner-Weir, S. GLP-1/exendin-4 facilitates beta-cell neogenesis in rat and human pancreatic ducts. Diabetes Res. Clin. Pract. 73(1):107-110; 2006.
68. Young, J.; Sukhova, G.; Foster, D.; Kisiel, W.; Libby, P.; Schonbeck, U. The serpin proteinase inhibitor 9 is an endogenous inhibitor of interleukin 1beta-converting enzyme (caspase-1) activity in human vascular smooth muscle cells. J. Exp. Med. 191(9):1535-1544; 2000.