Recovery of Islet β-Cell Function in Streptozotocin- Induced Diabetic Mice

Abstract

Limitations in islet β-cell transplantation as a therapeutic option for type 1 diabetes have prompted renewed interest in islet regeneration as a source of new islets. In this study we tested whether severely diabetic adult C57BL/6 mice can regenerate β-cells. Diabetes was induced in C57BL/6 mice with high-dose streptozotocin (160−170 mg/kg). In the absence of islet transplantation, all diabetic mice remained diabetic (blood glucose >400 mg/dl), and no spontaneous reversal of diabetes was observed. When syngeneic islets (200/mouse) were transplanted into these diabetic mice under a single kidney capsule, stable restoration of euglycemia for ≥120 days was achieved. Removal of the kidney bearing the transplanted islets at 120 days posttransplantation revealed significant restoration of endogenous β-cell function. This restoration of islet function was associated with increased β-cell mass, as well as β-cell hypertrophy and proliferation. The restoration of islet cell function was facilitated by the presence of a spleen; however, the facilitation was not due to the direct differentiation of spleen-derived cells into β-cells. This study supports the possibility of restoring β-cell function in diabetic individuals and points to a role for the spleen in facilitating this process.