Islet Transplantation in Diabetic NSG Mice

After induction of diabetes by intraperitoneal injection of 180 mg/kg body weight streptozotocin, diabetic NSG mice (blood glucose levels >350 mg/dl) received native NPICCs (3000, 1500, or 750 IEQs/mouse) or REPIs (750 or 1500 IEQs/mouse) under the left kidney capsule as described recently (22 (link), 26 (link)). 3000 IEQs represent the standard dose of NPICCs for transplantation to achieve normoglycemia in about 80% of diabetic NSG mice. Blood glucose levels were monitored by FreeStyle Lite blood glucose test strips (Abbott, Wiesbaden, Germany). Diabetic mice with blood glucose levels >300 mg/dl were treated with insulin glargine (0.25–1 IE s.c. daily). Our primary endpoint was normoglycemia. The observation period was set to a maximum of 16 weeks. We used a stringent definition for normoglycemia which was specified as achievement of pretransplant glycemia (persistent random non-fasting blood glucose levels <120 mg/dl). This cut-off is based on the measurement of non-fasting blood glucose levels of untreated NSG mice (n = 107; 94.6 ± 15.2 mg/dl, range 62–128 mg/dl). In this control cohort there was no animal with non-fasting blood glucose levels above 120 mg/dl on two consecutive days. Because other studies often used non-fasting blood glucose levels <180 mg/dl to define normoglycemia after islet transplantation this threshold was also analyzed.