Improved function and proliferation of adult human beta cells engrafted in diabetic immunodeficient NOD-scid IL2rγ^null mice treated with alogliptin

Figures & data

Table 1 Demographic characteristics of human islet donors

	Donor 1	Donor 2	Donor 3
Age, years	51	53	65
Sex (M/F)	F	nr	M
Body weight, kg	69.0	nr	nr
BMI, kg/m^2	23.9	27.3	24.5

Abbreviations: BMI, body mass index; F, female; M, male; nr, not recorded.

Figure 1 Comparison of blood glucose and body weights of control and alogliptin-treated mice engrafted with human islets.

Notes: Diabetic NSG mice were transplanted with human islets from three individual donors and treated daily by gavage with alogliptin (n=5, each donor) or vehicle control (n=5, each donor). (A) Blood glucose and (B) body weight of the mice were monitored over the treatment period on the days indicated; shown are mean ± standard error of the mean. *P<0.05.
Abbreviation: NSG, NOD-scid IL2rγ^null.

Figure 2 Comparison of glucose tolerance tests in control and alogliptin-treated mice engrafted with human islets.

Notes: Human islet engrafted mice were treated daily with alogliptin or vehicle control. (A) A glucose tolerance test was administered to mice engrafted with islets from Donors 1 and 2 at days 21 and 19, respectively, following islet transplantation. The glucose tolerance test on mice engrafted with Donor 3 islets was administered at day 31 when the blood glucose of vehicle control mice was approaching normoglycemia. *P<0.05. (B) Glucose AUC for the 120 min glucose tolerance test shown in (A); n=4 mice per group for each donor; shown are mean ± standard error of the mean.
Abbreviations: AUC, area under the curve; NS, not significant.

Figure 3 Comparison of human insulin and C-peptide levels in control and alogliptin-treated mice engrafted with human islets.

Notes: Non-fasting blood was collected from NSG mice engrafted with human islets from Donors 2 and 3 on days 26 and 24, respectively, following transplant. Plasma levels of (A) human insulin and (B) human C-peptide from individual vehicle control (n=8 total, 4 per islet donor) or alogliptin-treated (n=7 total, 4 from Donor 2, and 3 from Donor 3) mice are shown. Plasma samples from mice engrafted with islets from Donor 1 were not available for analysis. Each dot or triangle represents data obtained from an individual mouse engrafted with human islets from Donors 2 or 3, respectively; horizontal bar indicates the mean for each group.
Abbreviation: NSG, NOD-scid IL2rγ^null.

Figure 4 Induction of human beta cell proliferation with alogliptin treatment of islet engrafted mice. Percent human beta cell proliferation in islet grafts from vehicle control (n=6 total, 2 per islet donor) and alogliptin-treated (n=6 total) mice.

Note: Each dot represents data obtained from a single islet graft from one mouse.
Abbreviation: BrdU, bromodeoxyuridine.

Figure 5 Insulin+BrdU+ beta cells in human islet grafts from alogliptin-treated mice.

Notes: Representative micrographs of human islets from a single donor (Donor 1) engrafted in (A) vehicle control or (B) alogliptin-treated mice are shown. Top panels show insulin (red) and BrdU (green) staining; bottom panels include nuclei staining with DAPI (blue). Similar results were seen with islet grafts from Donors 2 and 3. Arrows show insulin+BrdU+ cells; arrowheads indicate insulin-negative BrdU+ cells; cells were only counted as insulin+ if the staining was visible around the entire perimeter of the nucleus.
Abbreviations: BrdU, bromodeoxyuridine; DAPI, 4′,6-diamidino-2-phenylindole.