Functional properties of proislet isografts in diabetic mice

Abstract

Fetal proislets (islet precursors) were transplanted to isogeneic diabetic CBA/H mice for analysis of their development and function post-transplant. Immunohistochemically, proislets contained scattered populations of insulin-, glucagon- and somatostatin-producing cells; following isotransplantation proislets developed into mature islet tissue with normal endocrine cell composition. Proislet isografts also developed normal endocrine function after transplantation to diabetic mice. Isografts of eight and four donor-equivalents of proislets reversed streptozotocin-induced diabetes by 30 +/- 7 and 74 +/- 26 days, respectively. Following stimulation with intragastric glucose (50 mg) mice carrying established isografts of four donor-equivalents of proislets exhibited normal blood glucose responses; those grafted with eight donor-equivalents of proislets showed decreased blood glucose levels. The beta cell mass of proislets continued to grow and differentiate post-transplant; established proislet grafts contained greater than 100-fold the total insulin content of the corresponding number of fetal pancreases from which the proislets were derived. The mean insulin content of eight and four donor-equivalent proislet grafts was 231% and 156%, respectively, that of the mean content of adult mouse pancreas. The data show that glucose homeostasis can be restored in diabetic mice following isotransplantation of fetal proislets and that the quantity of tissue transplanted is a critical parameter in achieving optimal control.