Fig. 2.

Improved glycemic control in diabetic mice transplanted with WT islets treated with a Y1 receptor antagonist. a Alloxan-induced diabetic mice were transplanted with an optimal number of WT islets (300) (n = 6) or 60 WT islets (n = 12) and treated daily with either 0.5 μM BIBO3304 (n = 6) or placebo (n = 6) for 9 days, respectively, after which BIBO3304 treatment was stopped but blood glucose levels continuously monitored till day 60 post-transplant. b Results for the first 9 days expressed as area under the curve. c, d, g, h Diabetic mice were transplanted with 60 WT islets and subsequently orally treated with 0.5 μM BIBO3304 or placebo and i.v. glucose tolerance tests (1 g/kg body weight) (n = 4 per group) were performed at day 5 post-transplant. Blood glucose levels and insulin production were monitored. Results are also expressed as area under the curve. e Representative photomicrographs of islet transplant grafts from placebo and BIBO3304-treated mice showing immunofluorescent staining for insulin (red), Ki67 (green) and nucleus counterstained with DAPI (blue). Arrows indicate Ki67-positive β-cells. f Quantification of Ki67-positive β-cells in grafts of placebo or BIBO3304-treated mice (n = 3). i, j Diabetic mice were transplanted with 60 WT islets (n = 10 per group) and half of the mice were treated with 0.5 μM BIBO3304 from day 1, and the other half were treated with placebo. Mice originally receiving placebo were then treated with 0.5 μM BIBO3304 from day 9 for 10 days, after which treatment was discontinued. Blood glucose levels were monitored till day 60 after which survival nephrectomy was performed. k Diabetic mice were transplanted with 60 WT islets (n = 10) and treated with 0.5 μM BIBO3304 for 9 days after which treatment was discontinued. Blood glucose levels were monitored till day 260 after which survival nephrectomy was performed. Data are shown as mean ± s.e.m. *P < 0.05, **P < 0.01, calculated by t-test (b, d, f, h) or two-way ANOVA analysis