{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T07:43:44Z","timestamp":1779349424157,"version":"3.51.4"},"reference-count":63,"publisher":"American Diabetes Association","issue":"9","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,9,1]]},"abstract":"<jats:p>Successful islet transplantation depends on the infusion of sufficiently large quantities of islets, but only a small fraction of implanted islets become engrafted. The underlying mechanisms remain elusive. To probe the mechanism of islet revascularization, we determined the effect of angiopoietin-1 (Ang-1), a proangiogenic and antiapoptotic factor, on the survival, function, and revascularization of transplanted islets using a syngeneic model. Islets were transduced with adenoviruses expressing Ang-1 or control LacZ, followed by transplantation under the renal capsule. Diabetic mice receiving a marginal mass of 150 islets pretransduced with Ang-1 vector exhibited near normoglycemia posttransplantation. In contrast, diabetic mice receiving an equivalent islet mass pretransduced with control vector remained hyperglycemic. At 30 days posttransplantation, mice were killed and islet grafts retrieved for immunohistochemistry. Islet grafts with elevated Ang-1 production retained significantly increased microvascular density, improved glucose profiles, and increased glucose-stimulated insulin release. Cultured islets expressing Ang-1 displayed improved viability and enhanced glucose-stimulated insulin secretion in the presence of cytokines. In contrast, control islets exhibited increased apoptosis and diminished glucose-stimulated insulin release in response to cytokine treatment. These results indicate that Ang-1 confers a cytoprotective effect on islets, enhancing islet engraftment and preserving functional islet mass in transplants.<\/jats:p>","DOI":"10.2337\/db07-0371","type":"journal-article","created":{"date-parts":[[2007,8,28]],"date-time":"2007-08-28T17:28:04Z","timestamp":1188322084000},"page":"2274-2283","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":53,"title":["Angiopoietin-1 Production in Islets Improves Islet Engraftment and Protects Islets From Cytokine-Induced Apoptosis"],"prefix":"10.2337","volume":"56","author":[{"given":"Dongming","family":"Su","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Rangos Research Center, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Rangos Research Center, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shen","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Rangos Research Center, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Slusher","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Rangos Research Center, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Bottino","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Rangos Research Center, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne","family":"Bertera","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Rangos Research Center, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Bromberg","sequence":"additional","affiliation":[{"name":"Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. Henry","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Rangos Research Center, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031208190153000_R1","doi-asserted-by":"crossref","unstructured":"Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV: Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med\u2008343:230\u2013238,2000","DOI":"10.1056\/NEJM200007273430401"},{"key":"2022031208190153000_R2","doi-asserted-by":"crossref","unstructured":"Shapiro AM, Ricordi C, Hering BJ, Auchincloss H, Lindblad R, Robertson RP, Secchi A, Brendel MD, Berney T, Brennan DC, Cagliero E, Alejandro R, Ryan EA, DiMercurio B, Morel P, Polonsky KS, Reems JA, Bretzel RG, Bertuzzi F, Froud T, Kandaswamy R, Sutherland DE, Eisenbarth G, Segal M, Preiksaitis J, Korbutt GS, Barton FB, Viviano L, Seyfert-Margolis V, Bluestone J, Lakey JR: International trial of the Edmonton protocol for islet transplantation. N Engl J Med\u2008355:1318\u20131330,2006","DOI":"10.1056\/NEJMoa061267"},{"key":"2022031208190153000_R3","doi-asserted-by":"crossref","unstructured":"Boker A, Rothenberg L, Hernandez C, Kenyon NS, Ricordi C, Alejandro R: Human islet transplantation: update. World J Surg\u200825:481\u2013486,2001","DOI":"10.1007\/s002680020341"},{"key":"2022031208190153000_R4","unstructured":"Shapiro J: Eighty years after insulin: parallels with modern islet transplantation. CMAJ\u2008167:1398\u20131400,2002"},{"key":"2022031208190153000_R5","doi-asserted-by":"crossref","unstructured":"Ryan EA, Lakey JR, Paty BW, Imes S, Korbutt GS, Knetema NM, Bigam D, Rajotte RV, Shapiro AM: Successful islet transplantation: continued insulin reserve provides long-term glycemic control. Diabetes\u200851:2148\u20132157,2002","DOI":"10.2337\/diabetes.51.7.2148"},{"key":"2022031208190153000_R6","doi-asserted-by":"crossref","unstructured":"Ryan EA, Paty BW, Senior PA, Bigam D, Alfadhli E, Kneteman NM, Lakey JR, Shapiro AM: Five-year follow-up after clinical islet transplantation. Diabetes\u200854:2060\u20132069,2005","DOI":"10.2337\/diabetes.54.7.2060"},{"key":"2022031208190153000_R7","doi-asserted-by":"crossref","unstructured":"Zhang N, Bertera S, Qu S, He J, Su D, Bottino R, Bromberg J, Dong HH: Therapeutic angiogenesis for islet revascularization. Immunology, Endocrine and Metabolic Agents in Medicinal Chemistry\u20086:155\u2013166,2006","DOI":"10.2174\/187152206776359939"},{"key":"2022031208190153000_R8","doi-asserted-by":"crossref","unstructured":"Kampf C, Carlsson P-O: Physiology of islet engraftment. Immunology, Endocrine and Metabolic Agents in Medicinal Chemistry\u20086:167\u2013178,2006","DOI":"10.2174\/187152206776359902"},{"key":"2022031208190153000_R9","doi-asserted-by":"crossref","unstructured":"Menger MD, Yamauchi J-I, Vollmar B: Revascularization and microcirculation of freshly grafted islets of Langerhans. World J Surg\u200825:509\u2013515,2001","DOI":"10.1007\/s002680020345"},{"key":"2022031208190153000_R10","doi-asserted-by":"crossref","unstructured":"Carlsson PO, Palm F, Andersson A, Liss P: Markedly decreased oxygen tension in transplanted rat pancreatic islets irrespective of implantation sites. Diabetes\u200850:489\u2013495,2001","DOI":"10.2337\/diabetes.50.3.489"},{"key":"2022031208190153000_R11","doi-asserted-by":"crossref","unstructured":"Mattsson G, Jansson L, Carlsson PO: Decreased vascular density in mouse pancreatic islets after transplantation. Diabetes\u200851:1362\u20131366,2002","DOI":"10.2337\/diabetes.51.5.1362"},{"key":"2022031208190153000_R12","doi-asserted-by":"crossref","unstructured":"Jansson L, Carlsson PO: Graft vascular function after transplantation of pancreatic islets. Diabetologia\u200845:749\u2013763,2002","DOI":"10.1007\/s00125-002-0827-4"},{"key":"2022031208190153000_R13","doi-asserted-by":"crossref","unstructured":"Mattsson G, Jansson L, Nordin A, Andersson A, Carlsson PO: Evidence of functional impairment of syngerneically transplanted mouse pancreatic islets retrieved from the liver. Diabetes\u200853:948\u2013954,2004","DOI":"10.2337\/diabetes.53.4.948"},{"key":"2022031208190153000_R14","unstructured":"Zhang N, Anthony K, Shinozaki K, Altomonte J, Bloomgarden Z, Dong H: Angiogenic gene therapy for improving islet graft vascularization. Gene Ther Mol Biol\u20087:153\u2013165,2003"},{"key":"2022031208190153000_R15","doi-asserted-by":"crossref","unstructured":"Zhang N, Richter A, Suriawinata J, Cong L, Zhang H, Altomonte J, Song K, Meseck M, Bromberg J, Dong H: Elevated vascular endothelial growth factor production in islets improves islet graft vascularization. Diabetes\u200853:963\u2013970,2004","DOI":"10.2337\/diabetes.53.4.963"},{"key":"2022031208190153000_R16","doi-asserted-by":"crossref","unstructured":"Lai Y, Schneider D, Kidszun A, Hauck-Schmalenberger I, Breier G, Brandhorst D, Brandhorst H, Iken M, Brendel MD, Bretzel RG, Linn T: Vascular endothelial growth factor increases functional beta-cell mass by improvement of angiogenesis of isolated human and murine pancreatic islets. Transplantation\u200879:1530\u20131536,2005","DOI":"10.1097\/01.TP.0000163506.40189.65"},{"key":"2022031208190153000_R17","doi-asserted-by":"crossref","unstructured":"Sigrist S, Mechine-Neuville A, Mandes K, Calenda V, Braun S, Legeay G, Bellocq JP, Pinget M, Kessler L: Influence of VEGF on the viability of encapsulated pancreatic rat islets after transplantation in diabetic mice. Cell Transplant\u200812:627\u2013635,2003","DOI":"10.3727\/000000003108747109"},{"key":"2022031208190153000_R18","doi-asserted-by":"crossref","unstructured":"Linn T, Schneider K, Hammes HP, Preissner KT, Brandhorst H, Morgenstern E, Kiefer F, Bretzel RG: Angiogenic capacity of endothelial cells in islets of Langerhans. Faseb J\u200817:881\u2013883,2003","DOI":"10.1096\/fj.02-0615fje"},{"key":"2022031208190153000_R19","doi-asserted-by":"crossref","unstructured":"Brissova M, Fowler M, Wiebe P, Shostak A, Shiota M, Radhika A, Lin PC, Gannon M, Powers AC: Intraislet endothelial cells contribute to revascularization of transplanted pancreatic islets. Diabetes\u200853:1318\u20131325,2004","DOI":"10.2337\/diabetes.53.5.1318"},{"key":"2022031208190153000_R20","doi-asserted-by":"crossref","unstructured":"Nyqvist D, Kohler M, Wahlstedt H, Berggren PO: Donor islet endothelial cells participate in formation of functional vessels within pancreatic islet grafts. Diabetes\u200854:2287\u20132293,2005","DOI":"10.2337\/diabetes.54.8.2287"},{"key":"2022031208190153000_R21","doi-asserted-by":"crossref","unstructured":"Olsson R, Carlsson PO: The pancreatic islet endothelial cell: emerging roles in islet function and disease. Int J Biochem Cell Biol\u200838:710\u2013714,2006","DOI":"10.1016\/j.biocel.2006.02.004"},{"key":"2022031208190153000_R22","doi-asserted-by":"crossref","unstructured":"Brissova M, Shostak A, Shiota M, Wiebe PO, Poffenberger G, Kantz J, Chen Z, Carr C, Jerome WG, Chen J, Baldwin HS, Nicholson W, Bader DM, Jetton T, Gannon M, Powers AC: Pancreatic islet production of vascular endothelial growth factor\u2013A is essential for islet vascularization, revascularization, and function. Diabetes\u200855:2974\u20132985,2006","DOI":"10.2337\/db06-0690"},{"key":"2022031208190153000_R23","doi-asserted-by":"crossref","unstructured":"Colen KL, Crisera CA, Rose MI, Connelly PR, Longaker MT, Gittes GK: Vascular development in the mouse embryonic pancreas and lung. J Pediatr Surg\u200834:781\u2013785,1999","DOI":"10.1016\/S0022-3468(99)90373-1"},{"key":"2022031208190153000_R24","doi-asserted-by":"crossref","unstructured":"Jones PF: Not just angiogenesis: wider roles for the angiopoietins. J Pathol\u2008201:515\u2013527,2003","DOI":"10.1002\/path.1452"},{"key":"2022031208190153000_R25","doi-asserted-by":"crossref","unstructured":"Brindle NP, Saharinen P, Alitalo K: Signaling and functions of angiopoietin-1 in vascular protection. Circ Res\u200898:1014\u20131023,2006","DOI":"10.1161\/01.RES.0000218275.54089.12"},{"key":"2022031208190153000_R26","doi-asserted-by":"crossref","unstructured":"Kwak HJ, So JN, Lee SJ, Kim I, Koh GY: Angiopoietin-1 is an apoptosis survival factor for endothelial cells. FEBS Lett\u2008448:249\u2013253,1999","DOI":"10.1016\/S0014-5793(99)00378-6"},{"key":"2022031208190153000_R27","doi-asserted-by":"crossref","unstructured":"Dumont DJ, Gradwohl G, Fong GH, Puri MC, Gertsenstein M, Auerbach A, Breitman ML: Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo. Genes Dev\u20088:1897\u20131909,1994","DOI":"10.1101\/gad.8.16.1897"},{"key":"2022031208190153000_R28","doi-asserted-by":"crossref","unstructured":"Sato TN, Tozawa Y, Deutsch U, Wolburg-Buchholz K, Fujiwara Y, Gendron-Maguire M, Gridley T, Wolburg H, Risau W, Qin Y: Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature\u2008376:70\u201374,1995","DOI":"10.1038\/376070a0"},{"key":"2022031208190153000_R29","doi-asserted-by":"crossref","unstructured":"Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN, Yancopoulos GD: Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell\u200887:1171\u20131180,1996","DOI":"10.1016\/S0092-8674(00)81813-9"},{"key":"2022031208190153000_R30","doi-asserted-by":"crossref","unstructured":"Suri C, McClain J, Thurston G, McDonald DM, Zhou H, Oldmixon EH, Sato TN, Yancopoulos GD: Increased vascularization in mice overexpressing angiopoietin-1. Science\u2008282:468\u2013471,1998","DOI":"10.1126\/science.282.5388.468"},{"key":"2022031208190153000_R31","doi-asserted-by":"crossref","unstructured":"Thurston G, Suri C, Smith K, McClain J, Sato TN, Yancopoulos GD, McDonald DM: Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science\u2008286:2511\u20132514,1999","DOI":"10.1126\/science.286.5449.2511"},{"key":"2022031208190153000_R32","doi-asserted-by":"crossref","unstructured":"Kanda S, Miyata Y, Mochizuki Y, Matsuyama T, Kanetake H: Angiopoietin 1 is mitogenic for cultured endothelial cells. Cancer Res\u200865:6820\u20136827,2005","DOI":"10.1158\/0008-5472.CAN-05-0522"},{"key":"2022031208190153000_R33","doi-asserted-by":"crossref","unstructured":"Garcia-Ocana A, Takane KK, Reddy VT, Lopez-Talavera J-C, Vasavada RC, Stewart AF: Adenovirus-mediated hepatocyte growth factor expression in mouse islets improves pancreatic islet transplantation performance and reduces beta cell death. J Biol Chem\u2008278:343\u2013351,2003","DOI":"10.1074\/jbc.M207848200"},{"key":"2022031208190153000_R34","doi-asserted-by":"crossref","unstructured":"Altomonte J, Richter A, Harbaran S, Suriawinata J, Nakae J, Thung SN, Meseck M, Accili D, Dong H: Inhibition of Foxo1 function is associated with improved fasting glycemia in diabetic mice. Am J Physiol\u2008285:E718\u2013E728,2003","DOI":"10.1152\/ajpendo.00156.2003"},{"key":"2022031208190153000_R35","doi-asserted-by":"crossref","unstructured":"Yang Z, Chen M, Ellett JD, Carter JD, Brayman KL, Nadler JL: Inflammatory blockade improves human pancreatic islet function and viability. Am J Transplant\u20085:475\u2013483,2005","DOI":"10.1111\/j.1600-6143.2005.00707.x"},{"key":"2022031208190153000_R36","doi-asserted-by":"crossref","unstructured":"Cory S, Adams JM: The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer\u20082:647\u2013656,2002","DOI":"10.1038\/nrc883"},{"key":"2022031208190153000_R37","doi-asserted-by":"crossref","unstructured":"Collier JJ, Fueger PT, Hohmeier HE, Newgard CB: Pro- and antiapoptotic proteins regulate apoptosis but do not protect against cytokine-mediated cytotoxicity in rat islets and \u03b2-cell lines. Diabetes\u200855:1398\u20131406,2006","DOI":"10.2337\/db05-1000"},{"key":"2022031208190153000_R38","doi-asserted-by":"crossref","unstructured":"Delaney CA, Pavlovic D, Hoorens A, Pipeleers DG, Eizirik DL: Cytokines induce deoxyribonucleic acid strand breaks and apoptosis in human pancreatic islet cells. Endocrinology\u2008138:2610\u20132614,1997","DOI":"10.1210\/endo.138.6.5204"},{"key":"2022031208190153000_R39","doi-asserted-by":"crossref","unstructured":"Harfouche R, Hassessian HM, Guo Y, Faivre V, Srikant CB, Yancopoulos GD, Hussain SN: Mechanisms which mediate the antiapoptotic effects of angiopoietin-1 on endothelial cells. Microvasc Res\u200864:135\u2013147,2002","DOI":"10.1006\/mvre.2002.2421"},{"key":"2022031208190153000_R40","doi-asserted-by":"crossref","unstructured":"Harfouche R, Gratton JP, Yancopoulos GD, Noseda M, Karsan A, Hussain SN: Angiopoietin-1 activates both anti- and proapoptotic mitogen-activated protein kinases. Faseb J\u200817:1523\u20131525,2003","DOI":"10.1096\/fj.02-0698fje"},{"key":"2022031208190153000_R41","doi-asserted-by":"crossref","unstructured":"Daly C, Wong V, Burova E, Wei Y, Zabski S, Griffiths J, Lai KM, Lin HC, Ioffe E, Yancopoulos GD, Rudge JS: Angiopoietin-1 modulates endothelial cell function and gene expression via the transcription factor FKHR (FOXO1). Genes Dev\u200818:1060\u20131071,2004","DOI":"10.1101\/gad.1189704"},{"key":"2022031208190153000_R42","doi-asserted-by":"crossref","unstructured":"Dallabrida SM, Ismail N, Oberle JR, Himes BE, Rupnick MA: Angiopoietin-1 promotes cardiac and skeletal myocyte survival through integrins. Circ Res\u200896:e8\u2013e24,2005","DOI":"10.1161\/01.RES.0000158285.57191.60"},{"key":"2022031208190153000_R43","doi-asserted-by":"crossref","unstructured":"Valable S, Bellail A, Lesne S, Liot G, Mackenzie ET, Vivien D, Bernaudin M, Petit E: Angiopoietin-1-induced PI3-kinase activation prevents neuronal apoptosis. Faseb J\u200817:443\u2013445,2003","DOI":"10.1096\/fj.02-0372fje"},{"key":"2022031208190153000_R44","doi-asserted-by":"crossref","unstructured":"Weber CC, Cai H, Ehrbar M, Kubota H, Martiny-Baron G, Weber W, Djonov V, Weber E, Mallik AS, Fussenegger M, Frei K, Hubbell JA, Zisch AH: Effects of protein and gene transfer of the angiopoietin-1 fibrinogen-like receptor-binding domain on endothelial and vessel organization. J Biol Chem\u2008280:22445\u201322453,2005","DOI":"10.1074\/jbc.M410367200"},{"key":"2022031208190153000_R45","doi-asserted-by":"crossref","unstructured":"Cascone I, Napione L, Maniero F, Serini G, Bussolino F: Stable interaction between alpha5beta1 integrin and Tie2 tyrosine kinase receptor regulates endothelial cell response to Ang-1. J Cell Biol\u2008170:993\u20131004,2005","DOI":"10.1083\/jcb.200507082"},{"key":"2022031208190153000_R46","doi-asserted-by":"crossref","unstructured":"Carlson TR, Feng Y, Maisonpierre PC, Mrksich M, Morla AO: Direct cell adhesion to the angiopoietins mediated by integrins. J Biol Chem\u2008276:26516\u201326525,2001","DOI":"10.1074\/jbc.M100282200"},{"key":"2022031208190153000_R47","doi-asserted-by":"crossref","unstructured":"Bosco D, Meda P, Halban PA, Rouiller DG: Importance of cell-matrix interactions in rat islet \u03b2-cell secretion in vitro: role of \u03b16\u03b21 integrin. Diabetes\u200849:233\u2013243,2000","DOI":"10.2337\/diabetes.49.2.233"},{"key":"2022031208190153000_R48","doi-asserted-by":"crossref","unstructured":"Yashpal NK, Li J, Wheeler MB, Wang R: Expression of {beta}1 integrin receptors during rat pancreas development: sites and dynamics. Endocrinology\u2008146:1798\u20131807,2005","DOI":"10.1210\/en.2004-1292"},{"key":"2022031208190153000_R49","doi-asserted-by":"crossref","unstructured":"Hammar E, Parnaud G, Bosco D, Perriraz N, Maedler K, Donath M, Rouiller DG, Halban PA: Extracellular matrix protects pancreatic \u03b2-cells against apoptosis: role of short- and long-term signaling pathways. Diabetes\u200853:2034\u20132041,2004","DOI":"10.2337\/diabetes.53.8.2034"},{"key":"2022031208190153000_R50","doi-asserted-by":"crossref","unstructured":"Parnaud G, Hammar E, Rouiller DG, Armanet M, Halban PA, Bosco D: Blockade of \u03b21 integrin\u2013laminin-5 interaction affects spreading and insulin secretion of rat \u03b2-cells attached on extracellular matrix. Diabetes\u200855:1413\u20131420,2006","DOI":"10.2337\/db05-1388"},{"key":"2022031208190153000_R51","doi-asserted-by":"crossref","unstructured":"Kallskog O, Kampf C, Andersson A, Carlsson PO, Hansell P, Johansson M, Jansson L: Lymphatic vessels in pancreatic islets implanted under the renal capsule of rats. Am J Transplant\u20086:680\u2013686,2006","DOI":"10.1111\/j.1600-6143.2006.01234.x"},{"key":"2022031208190153000_R52","doi-asserted-by":"crossref","unstructured":"Ji RC: Lymphatic endothelial cells, lymphangiogenesis, and extracellular matrix. Lymphat Res Biol\u20084:83\u2013100,2006","DOI":"10.1089\/lrb.2006.4.83"},{"key":"2022031208190153000_R53","doi-asserted-by":"crossref","unstructured":"Cho CH, Sung HK, Kim KT, Cheon HG, Oh GT, Hong HJ, Yoo OJ, Koh GY: COMP-angiopoietin-1 promotes wound healing through enhanced angiogenesis, lymphangiogenesis, and blood flow in a diabetic mouse model. Proc Natl Acad Sci U S A\u2008103:4946\u20134951,2006","DOI":"10.1073\/pnas.0506352103"},{"key":"2022031208190153000_R54","doi-asserted-by":"crossref","unstructured":"Zhang N, Schroppel B, Chen D, Fu S, Hudkins KL, Zhang H, Murphy BM, Sung RS, Bromberg JS: Adenovirus transduction induces expression of multiple chemokines and chemokine receptors in murine beta cells and pancreatic islets. Am J Transplant\u20083:1230\u20131241,2003","DOI":"10.1046\/j.1600-6143.2003.00215.x"},{"key":"2022031208190153000_R55","doi-asserted-by":"crossref","unstructured":"Emamaullee JA, Shapiro AM: Interventional strategies to prevent \u03b2-cell apoptosis in islet transplantation. Diabetes\u200855:1907\u20131914,2006","DOI":"10.2337\/db05-1254"},{"key":"2022031208190153000_R56","doi-asserted-by":"crossref","unstructured":"Menger MD, Vajkoczy P, Beger C, Messmer K: Orientation of microvascular blood flow in pancreatic islet isografts. J Clin Invest\u200893:2280\u20132285,1994","DOI":"10.1172\/JCI117228"},{"key":"2022031208190153000_R57","doi-asserted-by":"crossref","unstructured":"Moberg L, Johansson H, Lukinius A, Berne C, Foss A, Kallen R, Ostraat O, Salmela K, Tibell A, Tufveson G, Elgue G, Nilsson Ekdahl K, Korsgren O, Nilsson B: Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet\u2008360:2039\u20132045,2002","DOI":"10.1016\/S0140-6736(02)12020-4"},{"key":"2022031208190153000_R58","doi-asserted-by":"crossref","unstructured":"Ozmen L, Ekdahl KN, Elgue G, Larsson R, Korsgren O, Nilsson B: Inhibition of thrombin abrogates the instant blood-mediated inflammatory reaction triggered by isolated human islets: possible application of the thrombin inhibitor melagatran in clinical islet transplantation. Diabetes\u200851:1779\u20131784,2002","DOI":"10.2337\/diabetes.51.6.1779"},{"key":"2022031208190153000_R59","doi-asserted-by":"crossref","unstructured":"Johansson U, Olsson A, Gabrielsson S, Nilsson B, Korsgren O: Inflammatory mediators expressed in human islets of Langerhans: implications for islet transplantation. Biochem Biophys Res Commun\u2008308:474\u2013479,2003","DOI":"10.1016\/S0006-291X(03)01392-5"},{"key":"2022031208190153000_R60","doi-asserted-by":"crossref","unstructured":"Desai NM, Goss JA, Deng S, Wolf BA, Markmann E, Palanjian M, Shock AP, Feliciano S, Brunicardi FC, Barker CF, Naji A, Markmann JF: Elevated portal vein drug levels of sirolimus and tacrolimus in islet transplant recipients: local immunosuppression or islet toxicity?Transplantation\u200876:1623\u20131625,2003","DOI":"10.1097\/01.TP.0000081043.23751.81"},{"key":"2022031208190153000_R61","doi-asserted-by":"crossref","unstructured":"Bell E, Cao X, Moibi JA, Greene SR, Young R, Trucco M, Gao Z, Matschinsky FM, Deng S, Markman JF, Naji A, Wolf BA: Rapamycin has a deleterious effect on MIN-6 cells and rat and human islets. Diabetes\u200852:2731\u20132739,2003","DOI":"10.2337\/diabetes.52.11.2731"},{"key":"2022031208190153000_R62","doi-asserted-by":"crossref","unstructured":"Shapiro AM, Gallant HL, Hao EG, Lakey JR, McCready T, Rajotte RV, Yatscoff RW, Kneteman NM: The portal immunosuppressive storm: relevance to islet transplantation?Ther Drug Monit\u200827:35\u201337,2005","DOI":"10.1097\/00007691-200502000-00008"},{"key":"2022031208190153000_R63","doi-asserted-by":"crossref","unstructured":"Zhang N, Su D, Qu S, Tse T, Bottino R, Balamurugan AN, Xu J, Bromberg JS, Dong HH: Sirolimus is associated with reduced islet engraftment and impaired \u03b2-cell function. Diabetes\u200855:2429\u20132436,2006","DOI":"10.2337\/db06-0173"}],"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/56\/9\/2274\/388721\/zdb00907002274.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/56\/9\/2274\/388721\/zdb00907002274.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:11:31Z","timestamp":1667405491000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/56\/9\/2274\/12605\/Angiopoietin-1-Production-in-Islets-Improves-Islet"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,9,1]]},"references-count":63,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2007,9,1]]}},"URL":"https:\/\/doi.org\/10.2337\/db07-0371","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,9,1]]}}}