Acceleration of chronic failure of intrahepatic canine islet autografts by a short course of prednisone

Transplantation. 1994 Jan;57(2):181-7. doi: 10.1097/00007890-199401001-00004.


A topic of current interest in islet transplantation is the selection of an optimal site for long-term graft survival since the intrahepatic site may be characterized by long-term failure. Additionally, the use of immunosuppressive agents such as prednisone may adversely affect long-term graft function. In this study, we examined the long-term outcome of intrahepatic canine islet autografts and compared this with results obtained in animals treated with a short-term course of steroids or steroids plus insulin. Islets were isolated using the automated method and were purified on discontinuous Euro-Collins Ficoll gradients (densities: 1.108, 1.096, 1.037). Prednisone-treated dogs were hyperglycemic during treatment but returned to normoglycemia after steroid withdrawal. Control and insulin-treated animals were normoglycemic following autotransplant, with no difference in plasma glucose levels between controls and the insulin-treated animals. All control dogs became diabetic at 11, 14, 17, and 19 months following islet autograft. Prednisone-treated dogs had more rapid onset of diabetes at 7, 11, and 12 months following ITx. Prednisone-treated dogs given insulin became hyperglycemic at 10, 14, 18, and 19 months post ITx. Graft failure was preceded by a decline in IVGTT Kg values and diminished insulin secretion. At the time of graft failure islets showed no lymphocytic infiltration and islets stained positive for glucagon but few insulin-containing cells were seen. Thus, even when an initially adequate B cell mass was transplanted, the intrahepatic site was characterized by long-term canine autograft failure. A short course of prednisone accelerated the time to graft failure and insulin treatment reversed this acceleration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Chronic Disease
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / surgery
  • Dogs
  • Female
  • Graft Rejection / chemically induced*
  • Graft Rejection / immunology
  • Insulin / administration & dosage
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans Transplantation / immunology*
  • Islets of Langerhans Transplantation / pathology
  • Liver / immunology
  • Liver / surgery
  • Male
  • Prednisone / administration & dosage
  • Prednisone / adverse effects*
  • Transplantation, Autologous


  • Blood Glucose
  • Insulin
  • Prednisone