ABB  Vol.3 No.6 A , October 2012
Prevention of beta cell death in chronic pancreatitis
ABSTRACT
Chronic pancreatitis is best described as a relentless, continuous inflammatory destruction of the pancreas parenchyma, characterized by irreversible destruction of the exocrine tissues, fibrosis, and at the late stage, the destruction of endocrine cells. Current therapies for chronic pancreatitis patients focus on pain relief by medical and minimally invasive endoscopic treatment as well as surgical management with resection of diseased parenchyma and drainage of obstructed ducts. Radical treatment of chronic pancreatitis has been successful with total pancreatictomy and islet autotransplantation (TP-IAT) that may prevent maladaptive intractable pain pathways and also avoid pancreatogenic diabetes in the well-selected patient. Distinct loss of pancreatic islet cells occurs in about 30%-50% of patients during the progression of chronic pancreatitis when severe fibrosis develops at the late stage of the disease. Profound β cell apoptosis induced by stresses encountered during islet isolation and transplantation further compromises β cell survival and function after TP-IAT. The molecular mechanisms that lead to β cell dysfunction in chronic pancreatitis remain largely undelineated. In this review, we summarize factors that may contribute β cell apoptosis during the disease progress and after TP-IAT and discuss potential interventional approaches that may prevent islet cell death during these processes. Such information is critical to the development of therapeutic protocols that can preserve the viability and function of β cell in patients with chronic pancreatitis.

Cite this paper
Dong, H. , Morgan, K. , Adams, D. and Wang, H. (2012) Prevention of beta cell death in chronic pancreatitis. Advances in Bioscience and Biotechnology, 3, 782-787. doi: 10.4236/abb.2012.326098.
References
[1]   R. Talukdar, N. Saikia, D.K. Singal, R. Tandon, Chronic pancreatitis: evolving paradigms, Pancreatology 6 (2006) 440-449.

[2]   E. Dixon, J.S. Graham, F. Sutherland, P.C. Mitchell, Splenic injury following endoscopic retrograde cholangiopancreatography: a case report and review of the literature, JSLS 8 (2004) 275-277.

[3]   N. Manciu, D.S. Beebe, P. Tran, R. Gruessner, D.E. Sutherland, K.G. Belani, Total pancreatectomy with islet cell autotransplantation: anesthetic implications, J Clin Anesth 11 (1999) 576-582.

[4]   J. Dixon, M. DeLegge, K.A. Morgan, D.B. Adams, Impact of total pancreatectomy with islet cell transplant on chronic pancreatitis management at a disease-based center, The American surgeon 74 (2008) 735-738.

[5]   D.C. Wahoff, B.E. Papalois, J.S. Najarian, D.M. Kendall, A.C. Farney, J.P. Leone, J. Jessurun, D.L. Dunn, R.P. Robertson, D.E. Sutherland, Autologous islet transplantation to prevent diabetes after pancreatic resection, Ann Surg 222 (1995) 562-575; discussion 575-569.

[6]   U.K. Bhanot, P. Moller, Mechanisms of parenchymal injury and signaling pathways in ectatic ducts of chronic pancreatitis: implications for pancreatic carcinogenesis, Lab Invest 89 (2009) 489-497.

[7]   H. Schrader, B.A. Menge, S. Schneider, O. Belyaev, A. Tannapfel, W. Uhl, W.E. Schmidt, J.J. Meier, Reduced pancreatic volume and beta-cell area in patients with chronic pancreatitis, Gastroenterology 136 (2009) 513-522.

[8]   R.M. Mitchell, M.F. Byrne, J. Baillie, Pancreatitis, Lancet 361 (2003) 1447-1455.

[9]   S. Mitnala, P.K. Pondugala, V.R. Guduru, P. Rabella, J. Thiyyari, S. Chivukula, S. Boddupalli, A.A. Hardikar, D.N. Reddy, Reduced expression of PDX-1 is associated with decreased beta cell function in chronic pancreatitis, Pancreas 39 (2010) 856-862.

[10]   A.M. Davalli, L. Scaglia, D.H. Zangen, J. Hollister, S. Bonner-Weir, G.C. Weir, Vulnerability of islets in the immediate posttransplantation period. Dynamic changes in structure and function, Diabetes 45 (1996) 1161-1167.

[11]   Y. Cui, D.K. Andersen, Pancreatogenic diabetes: special considerations for management, Pancreatology : official journal of the International Association of Pancreatology 11 (2011) 279-294.

[12]   P.G. Lankisch, Natural course of chronic pancreatitis, Pancreatology : official journal of the International Association of Pancreatology 1 (2001) 3-14.

[13]   A.C. Bateman, S.M. Turner, K.S. Thomas, P.R. McCrudden, D.R. Fine, P.A. Johnson, C.D. Johnson, J.P. Iredale, Apoptosis and proliferation of acinar and islet cells in chronic pancreatitis: evidence for differential cell loss mediating preservation of islet function, Gut 50 (2002) 542-548.

[14]   C. Hasel, B. Rau, S. Perner, J. Strater, P. Moller, Differential and mutually exclusive expression of CD95 and CD95 ligand in epithelia of normal pancreas and chronic pancreatitis, Laboratory investigation; a journal of technical methods and pathology 81 (2001) 317-326.

[15]   C. Hasel, S. Durr, B. Rau, J. Strater, R.M. Schmid, H. Walczak, M.G. Bachem, P. Moller, In chronic pancreatitis, widespread emergence of TRAIL receptors in epithelia coincides with neoexpression of TRAIL by pancreatic stellate cells of early fibrotic areas, Laboratory investigation; a journal of technical methods and pathology 83 (2003) 825-836.

[16]   S.E. Lamhamedi-Cherradi, S. Zheng, R.M. Tisch, Y.H. Chen, Critical roles of tumor necrosis factor-related apoptosis-inducing ligand in type 1 diabetes, Diabetes 52 (2003) 2274-2278.

[17]   U.K. Bhanot, P. Moller, Mechanisms of parenchymal injury and signaling pathways in ectatic ducts of chronic pancreatitis: implications for pancreatic carcinogenesis, Laboratory investigation; a journal of technical methods and pathology 89 (2009) 489-497.

[18]   M.A. Degli-Esposti, W.C. Dougall, P.J. Smolak, J.Y. Waugh, C.A. Smith, R.G. Goodwin, The novel receptor TRAIL-R4 induces NF-kappaB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain, Immunity 7 (1997) 813-820.

[19]   X. Chen, B. Ji, B. Han, S.A. Ernst, D. Simeone, C.D. Logsdon, NF-kappaB activation in pancreas induces pancreatic and systemic inflammatory response, Gastroenterology 122 (2002) 448-457.

[20]   A.E. Butler, J. Janson, S. Bonner-Weir, R. Ritzel, R.A. Rizza, P.C. Butler, Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes, Diabetes 52 (2003) 102-110.

[21]   M.Y. Donath, J. Storling, L.A. Berchtold, N. Billestrup, T. Mandrup-Poulsen, Cytokines and beta-cell biology: from concept to clinical translation, Endocrine reviews 29 (2008) 334-350.

[22]   R.K. Tandon, P.K. Garg, Oxidative stress in chronic pancreatitis: pathophysiological relevance and management, Antioxid Redox Signal 15 2757-2766.

[23]   P. Pavan Kumar, G. Radhika, G.V. Rao, R. Pradeep, C. Subramanyam, R. Talukdar, D.N. Reddy, M. Sasikala, Interferon gamma and glycemic status in diabetes associated with chronic pancreatitis, Pancreatology 12 65-70.

[24]   S. Mitnala, P.K. Pondugala, V.R. Guduru, P. Rabella, J. Thiyyari, S. Chivukula, S. Boddupalli, A.A. Hardikar, D.N. Reddy, Reduced expression of PDX-1 is associated with decreased beta cell function in chronic pancreatitis, Pancreas 39 856-862.

[25]   J.J. Blondet, A.M. Carlson, T. Kobayashi, T. Jie, M. Bellin, B.J. Hering, M.L. Freeman, G.J. Beilman, D.E. Sutherland, The role of total pancreatectomy and islet autotransplantation for chronic pancreatitis, The Surgical clinics of North America 87 (2007) 1477-1501, x.

[26]   J.L. Argo, J.L. Contreras, M.M. Wesley, J.D. Christein, Pancreatic resection with islet cell autotransplant for the treatment of severe chronic pancreatitis, The American surgeon 74 (2008) 530-536; discussion 536-537.

[27]   D.S. Nath, T.A. Kellogg, D.E. Sutherland, Total pancreatectomy with intraportal auto-islet transplantation using a temporarily exteriorized omental vein, Journal of the American College of Surgeons 199 (2004) 994-995.

[28]   M.D. Bellin, D.E. Sutherland, Pediatric islet autotransplantation: indication, technique, and outcome, Current diabetes reports 10 (2010) 326-331.

[29]   T. Kobayashi, J.C. Manivel, A.M. Carlson, M.D. Bellin, A. Moran, M.L. Freeman, G.J. Bielman, B.J. Hering, T. Dunn, D.E. Sutherland, Correlation of histopathology, islet yield, and islet graft function after islet autotransplantation in chronic pancreatitis, Pancreas 40 (2011) 193-199.

[30]   A.C. Farney, J.S. Najarian, R.E. Nakhleh, G. Lloveras, M.J. Field, P.F. Gores, D.E. Sutherland, Autotransplantation of dispersed pancreatic islet tissue combined with total or near-total pancreatectomy for treatment of chronic pancreatitis, Surgery 110 (1991) 427-437; discussion 437-429.

[31]   R.P. Robertson, K.J. Lanz, D.E. Sutherland, D.M. Kendall, Prevention of diabetes for up to 13 years by autoislet transplantation after pancreatectomy for chronic pancreatitis, Diabetes 50 (2001) 47-50.

[32]   M. Biarnes, M. Montolio, V. Nacher, M. Raurell, J. Soler, E. Montanya, Beta-cell death and mass in syngeneically transplanted islets exposed to short- and long-term hyperglycemia, Diabetes 51 (2002) 66-72.

[33]   Y.B. Ahn, G. Xu, L. Marselli, E. Toschi, A. Sharma, S. Bonner-Weir, D.C. Sgroi, G.C. Weir, Changes in gene expression in beta cells after islet isolation and transplantation using laser-capture microdissection, Diabetologia 50 (2007) 334-342.

[34]   A.M. Davalli, L. Scaglia, D.H. Zangen, J. Hollister, S. Bonner-Weir, G.C. Weir, Early changes in syngeneic islet grafts: effect of recipient's metabolic control on graft outcome, Transplantation proceedings 27 (1995) 3238-3239.

[35]   P. Bhardwaj, S. Thareja, S. Prakash, A. Saraya, Micronutrient antioxidant intake in patients with chronic pancreatitis, Tropical gastroenterology : official journal of the Digestive Diseases Foundation 25 (2004) 69-72.

[36]   J.T. Hsu, C.N. Yeh, T.L. Hwang, H.M. Chen, Y.Y. Jan, M.F. Chen, Outcome of pancreaticoduodenectomy for chronic pancreatitis, Journal of the Formosan Medical Association = Taiwan yi zhi 104 (2005) 811-815.

[37]   S.L. Ong, G. Gravante, C.A. Pollard, M.A. Webb, S. Illouz, A.R. Dennison, Total pancreatectomy with islet autotransplantation: an overview, HPB : the official journal of the International Hepato Pancreato Biliary Association 11 (2009) 613-621.

[38]   N. Howes, M.M. Lerch, W. Greenhalf, D.D. Stocken, I. Ellis, P. Simon, K. Truninger, R. Ammann, G. Cavallini, R.M. Charnley, G. Uomo, M. Delhaye, J. Spicak, B. Drumm, J. Jansen, R. Mountford, D.C. Whitcomb, J.P. Neoptolemos, Clinical and genetic characteristics of hereditary pancreatitis in Europe, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2 (2004) 252-261.

[39]   R.W. Ammann, Diagnosis and management of chronic pancreatitis: current knowledge, Swiss medical weekly 136 (2006) 166-174.

[40]   H.E. De Cock, M.A. Forman, T.B. Farver, S.L. Marks, Prevalence and histopathologic characteristics of pan-creatitis in cats, Veterinary pathology 44 (2007) 39-49.

[41]   H. Wang, C. Ferran, C. Attanasio, F. Calise, L.E. Otterbein, Induction of protective genes leads to islet survival and function, Journal of transplantation 2011 (2011) 141898.

[42]   H. Wang, H. Wu, F. Rocuts, Z. Gu, F.H. Bach, L.E. Otterbein, Activation of Peroxisome Proliferator-activated Receptor gamma Prolongs Islet Allograft Survival, Cell transplantation (2012).

[43]   J.A. Emamaullee, A.M. Shapiro, Interventional strategies to prevent beta-cell apoptosis in islet transplantation, Diabetes 55 (2006) 1907-1914.

[44]   S.T. Grey, M.B. Arvelo, W. Hasenkamp, F.H. Bach, C. Ferran, A20 inhibits cytokine-induced apoptosis and nuclear factor kappaB-dependent gene activation in islets, The Journal of experimental medicine 190 (1999) 1135-1146.

[45]   R. Riachy, B. Vandewalle, J. Kerr Conte, E. Moerman, P. Sacchetti, B. Lukowiak, V. Gmyr, T. Bouck-enooghe, M. Dubois, F. Pattou, 1,25-dihydroxyvitamin D3 protects RINm5F and human islet cells against cytokine-induced apoptosis: implication of the antiapoptotic protein A20, Endocrinology 143 (2002) 4809-4819.

[46]   G. Christoffersson, P.O. Carlsson, M. Phillipson, Intramuscular islet transplantation promotes restored islet vascularity, Islets 3 (2011) 69-71.

[47]   G. Basta, R. Calafiore, Immunoisolation of pancre-atic islet grafts with no recipient's immunosuppression: actual and future perspectives, Current diabetes reports 11 (2011) 384-391.

[48]   A. Fort, N. Fort, C. Ricordi, C.L. Stabler, Biohybrid devices and encapsulation technologies for engineering a bioartificial pancreas, Cell transplantation 17 (2008) 997-1003.

[49]   J.A. Giraldo, J.D. Weaver, C.L. Stabler, Tissue engineering approaches to enhancing clinical islet transplantation through tissue engineering strategies, Journal of diabetes science and technology 4 (2010) 1238-1247.

[50]   N. Trivedi, M. Keegan, G.M. Steil, J. Hollister-Lock, W.M. Hasenkamp, C.K. Colton, S. Bonner-Weir, G.C. Weir, Islets in alginate macrobeads reverse diabetes despite minimal acute insulin secretory responses, Transplantation 71 (2001) 203-211.

[51]   R. van Schilfgaarde, P. de Vos, Factors influencing the properties and performance of microcapsules for immunoprotection of pancreatic islets, Journal of molecular medicine 77 (1999) 199-205.

[52]   J.O. Sandberg, N. Olsson, R.C. Johnson, C. Hellerstrom, A. Andersson, Immunosuppression, macroencapsulation and ultraviolet-B irradiation as immunoprotection in porcine pancreatic islet xenotransplantation, Pharmacology & toxicology 76 (1995) 400-405.

[53]   J.M. Pollok, C. Ibarra, C.E. Broelsch, J.P. Vacanti, [Im-muno-isolation of xenogenic islands of Langerhans in a tissue engineered autologous cartilage capsule], Zentralblatt fur Chirurgie 123 (1998) 830-833.

[54]   M. Qi, Y. Gu, N. Sakata, D. Kim, Y. Shirouzu, C. Yamamoto, A. Hiura, S. Sumi, K. Inoue, PVA hydrogel sheet macroencapsulation for the bioartificial pancreas, Biomaterials 25 (2004) 5885-5892.

[55]   Y. Teramura, H. Iwata, Islets surface modification prevents blood-mediated inflammatory responses, Bioconjug Chem 19 (2008) 1389-1395.

[56]   D.Y. Lee, S.J. Park, S. Lee, J.H. Nam, Y. Byun, Highly poly(ethylene) glycolylated islets improve long-term islet allograft survival without immunosuppressive medication, Tissue Eng 13 (2007) 2133-2141.

[57]   A. Basarkar, J. Singh, Poly (lactide-co-glycolide)-polymethacrylate nanoparticles for intramuscular delivery of plasmid encoding interleukin-10 to prevent autoimmune diabetes in mice, Pharmaceutical research 26 (2009) 72-81.

[58]   G.H. Mao, G.A. Chen, H.Y. Bai, T.R. Song, Y.X. Wang, The reversal of hyperglycaemia in diabetic mice using PLGA scaffolds seeded with islet-like cells derived from human embryonic stem cells, Biomaterials 30 (2009) 1706-1714.

[59]   R. Jain, N.H. Shah, A.W. Malick, C.T. Rhodes, Controlled drug delivery by biodegradable poly(ester) devices: different preparative approaches, Drug development and industrial pharmacy 24 (1998) 703-727.

[60]   R.A. Jain, The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices, Biomaterials 21 (2000) 2475-2490.

[61]   J.M. Lu, X. Wang, C. Marin-Muller, H. Wang, P.H. Lin, Q. Yao, C. Chen, Current advances in research and clinical applications of PLGA-based nanotechnology, Expert review of molecular diagnostics 9 (2009) 325-341.

[62]   K.A. Athanasiou, G.G. Niederauer, C.M. Agrawal, Sterilization, toxicity, biocompatibility and clinical applications of polylactic acid/polyglycolic acid copolymers, Biomaterials 17 (1996) 93-102.

[63]   D. Yin, J.W. Ding, J. Shen, L. Ma, M. Hara, A.S. Chong, Liver ischemia contributes to early islet failure following intraportal transplantation: benefits of liver ischemic-preconditioning, American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 6 (2006) 60-68.

[64]   J.T. Wilson, E.L. Chaikof, Thrombosis and inflammation in intraportal islet transplantation: a review of pathophysiology and emerging therapeutics, Journal of diabetes science and technology 2 (2008) 746-759.

[65]   R. Cardani, A. Pileggi, C. Ricordi, C. Gomez, D.A. Baidal, G.G. Ponte, D. Mineo, R.N. Faradji, T. Froud, G. Ciancio, V. Esquenazi, G.W. Burke, 3rd, G. Selvaggi, J. Miller, N.S. Kenyon, R. Alejandro, Allosensitization of islet allograft recipients, Transplantation 84 (2007) 1413-1427.

[66]   M.R. Rickels, M. Kamoun, J. Kearns, J.F. Markmann, A. Naji, Evidence for allograft rejection in an islet transplant recipient and effect on beta-cell secretory capacity, The Journal of clinical endocrinology and metabolism 92 (2007) 2410-2414.

[67]   T. Lund, O. Korsgren, I.A. Aursnes, H. Scholz, A. Foss, Sustained reversal of diabetes following islet transplantation to striated musculature in the rat, The Journal of surgical research 160 (2010) 145-154.

[68]   A. Salazar-Banuelos, J.R. Wright, Jr., D. Sigalet, L. Benitez-Bribiesca, Pancreatic islet transplantation into the bone marrow of the rat, American journal of surgery 195 (2008) 674-678; discussion 678.

[69]   D.M. Berman, J.J. O'Neil, L.C. Coffey, P.C. Chaffanjon, N.M. Kenyon, P. Ruiz, Jr., A. Pileggi, C. Ricordi, N.S. Kenyon, Long-term survival of nonhuman primate islets implanted in an omental pouch on a biodegradable scaffold, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 9 (2009) 91-104.

[70]   D.J. van der Windt, G.J. Echeverri, J.N. Ijzermans, D.K. Cooper, The choice of anatomical site for islet transplantation, Cell transplantation 17 (2008) 1005-1014.

[71]   A. Pileggi, R.D. Molano, C. Ricordi, E. Zahr, J. Collins, R. Valdes, L. Inverardi, Reversal of diabetes by pancreatic islet transplantation into a subcutaneous, neovascularized device, Transplantation 81 (2006) 1318-1324.

 
 
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