Figure 6 |. Pyruvate carboxylase is required for the protective effects of glucose metabolism in human islets in vivo and their capacity to reverse diabetes in mice.
a, Schematic of marginal mass islet transplantation in diabetic NOD-SCID mice using human donor islets pre-treated with the indicated single or double combination of compounds for 24 h prior to transplantation. Islet grafts were excised at day 2 post transplantation for quantification of β-cell death as % insulin and TUNEL double positive cells with t-test statistic. Representative images are shown, scale bars are 10 microns. Data are from n=6 (Veh, BAD SAHBA SD), n=5 (RO0281675) and n=4 (BAD SAHBA SD + PAA, BAD SAHBA AAA) mice.
b, Blood glucose levels of mice treated as in (a) measured up to 53 days post transplantation. Nephrectomy was performed at day 50 to excise grafts and show the requirement of protected donor islets for improving blood glucose. Statistical comparisons are provided in Table 1. Data are from n=6 (Veh, BAD SAHBA SD), n=3 (RO0281675, BAD SAHBA SD + PAA) and n=4 (BAD SAHBA AAA) mice.
c, Human insulin levels in the sera of mice treated as in (a) on day 49 post transplantation. Data are from n=6 (Veh, BAD SAHBA SD), n=3 (RO0281675, BAD SAHBA SD + PAA) and n=4 (BAD SAHBA AAA) mice.
d, Mean blood glucose levels during an intraperitoneal glucose tolerance test (GTT) and corresponding area under the curve (AUC) in mice treated as in (a) on day 42 post transplantation. Number of mice per condition is as in (c).
Data are means ± s.e.m. from independent experiments with statistical analyses using one-way ANOVA with Tukey adjustment for multiple comparisons.