title: Relevance of hyperglycemia on the timing of functional loss of allogeneic islet transplants: implication for mouse model.
abstract: BACKGROUND
  The role of recipient hyperglycemia on timing of allograft survival is unknown. In this study, we investigated if and how variation in recipient glycemia affects the ability to achieve and maintain normoglycemia after transplant of C57BL/6 islets into diabetic BALB/c mice.
  
  
  RESULTS
  85 diabetic BALB/c mice with non-fasting glycaemia ranging between 275 and 600 mg/dL were transplanted with 400 C57BL/6 islets. The time of rejection inversely correlated with the pre-transplant blood glucose concentration (P=0.004). All the 13 mice with normoglycemia beyond 50 days had pretransplant glycemia <450 mg/dL and the presence of autologous beta cell function was demonstrated in 8 (>100 days function) by the persistence of normoglycemia after allograft removal. The presence of immunosuppression (rapamycin plus FK506 plus anti-IL-2Ra chain mAbs, n=31; rapamycin plus IL-10; n=29) removed the influence of pretransplant hyperglycemia but after treatment withdrawn the timing and the probability of graft loss correlate with the pretransplant hyperglycemia. Pretransplant glycemia was inversely correlated with HOMA-B and serum insulin showing that a significant residual beta cell mass was present in mice with glycemia <450 mg/dL.
  
  
  CONCLUSIONS
  This study demonstrates that the timing of functional loss of islets allotransplantation depends on the degree of recipient hyperglycemia. This potential bias should be kept in count in experimental results and a threshold that excludes moderate diabetes should be used in defining recipient's eligibility.
authors.affiliation: Immunology of Diabetes Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Melzi
authors.forename: Manuela
authors.initials: M
authors.lastname: Battaglia
authors.forename: Elena
authors.initials: E
authors.lastname: Draghici
authors.forename: Ezio
authors.initials: E
authors.lastname: Bonifacio
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Piemonti
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000473:pathology / Q000601:surgery; D004195:Disease Models, Animal; D005260:Female; D006943:Hyperglycemia / Q000150:complications* / Q000601:surgery*; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D015996:Survival Rate; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D001786:Blood Glucose