title: Nerve Growth Factor Improves Survival and Function of Transplanted Islets Via TrkA-mediated β Cell Proliferation and Revascularization.
abstract: BACKGROUND
  Nerve growth factor (NGF), which plays important roles in promoting growth and differentiation of nerve cells, has recently been reported as a regulator in pancreatic β cells in terms of insulin releasing function. In this study, we examined whether NGF stimulation would promote islet graft survival and function in islet transplantation.
  
  
  METHODS
  We found that supplementation of cultured islets with NGF improved the viability of islet cells and induced the production of insulin, vascular endothelial growth factor, and cellular proliferative markers. Because a specific inhibitor of TrkA, K252a, blocked all these effects, we propose that the TrkA receptor is the mediator of NGF stimulation.
  
  
  RESULTS
  After transplantation to the kidney subcapsule and liver of syngenic diabetic mice, a higher rate of normoglycemic achievement, increased serum insulin, and improved glucose tolerance were observed in the mice transplanted with NGF-pretreated islet grafts. Histological analysis revealed higher expression of insulin and vascular endothelial growth factor, an increase in proliferative β cells, and revascularization in NGF-pretreated islet grafts without activation of any inflammatory cells.
  
  
  CONCLUSIONS
  The NGF treatment can therefore serve as a new and promising therapeutic tool for improving islet graft viability and function in islet transplantation.
authors: 1 Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan. 2 Division of Integrated Surgery and Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan. 3 Division of International Cooperation for Disaster Medicine, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
authors: Tatsuo
authors: T
authors: Hata
authors: Naoaki
authors: N
authors: Sakata
authors: Gumpei
authors: G
authors: Yoshimatsu
authors: Haruyuki
authors: H
authors: Tsuchiya
authors: Masahiko
authors: M
authors: Fukase
authors: Masaharu
authors: M
authors: Ishida
authors: Takeshi
authors: T
authors: Aoki
authors: Yu
authors: Y
authors: Katayose
authors: Shinichi
authors: S
authors: Egawa
authors: Michiaki
authors: M
authors: Unno
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology / Q000628:therapy; D006085:Graft Survival / Q000187:drug effects; D026121:Indole Alkaloids / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D016381:Islets of Langerhans Transplantation / Q000379:methods* / Q000473:pathology / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D020932:Nerve Growth Factor / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020917:Receptor, trkA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D002227:Carbazoles; D016207:Cytokines; D026121:Indole Alkaloids; D018836:Inflammation Mediators; D007328:Insulin; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D020932:Nerve Growth Factor; C049985:staurosporine aglycone; D020917:Receptor, trkA