Eur J Anat, 4 (3): 149-159 (2000)

Islet morphology and function following foetal rat pancreatic transplantation

Muller C.J.F., Du Toit D.F., Page B.J., Louw J., Muller B.J.F., Williams K., Mattysen J.P., Lyners R.F.C.

Department of Anatomy, Faculty of Medicine, University of Stellenbosch, P.O. Box 19063, Tygerberg 7505, South Africa

ABSTRACT The restoration of endocrine and metabolic function remains the ultimate goal in the treatment of diabetes mellitus. Foetal pancreatic transplantation, because of the growth potential of especially the endocrine component, is an attractive method for endocrine replacement. Intravenous injection of 50 mg/kg streptozotocin into the tail vein of WAG rats resulted in the rapid onset of uncontrolled diabetes in 90% of recipients, requiring insulin support for survival. Transplantation of isogeneic (WAG ? WAG) foetal pancreata successfully reversed hyperglycaemia in 10 out of a group of 12 diabetic animals, lowering whole blood glucose levels from 13.47 ± 1.54 mmol/1 (with insulin support) to 7.63 ± 0.276 mmol/l (without insulin) within the first week post-transplantation. Other clinical features of diabetes were also reversed. At one and nine months post-transplantation, non-fasting whole blood glucose levels had normalised to 6.37 and 6.59 mmol/l (normal = 6.42 mmol/l). Intravenous glucose tolerance tests of the transplanted groups showed a return to basal values after 30 and 40 minutes respectively. Insulin secretion in response to glucose load yielded peak insulin values of 23.93 ?IU/l and 30.81 ?IU/l (normal = 70.93 ?IU/l), at one and nine months post-transplantation, compared to 3.18 ?IU/l of the diabetic controls. Histology of the grafts showed the presence of well-developed islets of Langerhans while the exocrine component had atrophied. Immunocytochemistry showed that the islets consisted mostly of insulin-positive ?-cells. Islet ?-cell volume of the grafts was not significantly different to the normal controls but morphometry showed a significant reduction in graft islet ?-cell volume and ?-cell size compared with normal pancreas islets of Langerhans. The results confirmed that although aberrations in the development of transplanted islets were noted, recipients of rat foetal pancreas transplants in this laboratory diabetic model were able to effectively reverse the clinical signs of diabetes in the short- and longer-term.

Keywords: glucose, insulin, streptozocin, animal experiment, animal model, animal tissue, article, cell size, cell structure, cell volume, controlled study, diabetes insipidus, fetus, glucose blood level, glucose tolerance test, hyperglycemia, immunocytochemistry, insulin release, Langerhans cell, morphometrics, nonhuman, pancreas islet beta cell, pancreas islet cell, pancreas transplantation, rat