Fig. 5.

GcgR mAb treatment promotes stable euglycemia in diabetic mice with human islet xenografts. A schematic of the study design using NSG-DTR islet recipients which received 1,000 IEQs of healthy human islets beneath the kidney capsule prior to induction of diabetes with diphtheria toxin to ablate endogenous mouse B cells (A). IHC, immunohistochemistry. Glycemic control (B–D) and insulin secretory responses (E and F) were assessed longitudinally (B), prior to cessation of mAb treatment (C and E), or following the metabolism of mAb after a washout period (D and F). Blood glucose and plasma insulin were assessed during fasting or after stimulation with glucose + l-arginine (C–F). Glucose tolerance test (GTT) was assessed after the washout period (G). Proliferation of α-cells and β-cells was assessed by coexpression of Ki67 with glucagon or insulin, respectively (H). n = 4 (saline + IgG); n = 5 (saline + GcgR mAb); n = 6 per each DT group; data are representative from three cadaveric donors. *P < 0.05 for GcgR mAb effect; †P < 0.05 for diptheria toxin effect. Standard error shown.