Figure 4.

Deletion of TRAF2 causes impaired glucose tolerance independent of Cre expression in the hypothalamus. (A) Non-fasted blood glucose levels in STZ-treated C57BL/6 recipients transplanted with 150 IEQs of WT (dotted line) and βTRAF2 (solid line) islets were determined. Data are representative of three independent mouse cohorts, in which 15 TRAF2_loxP/loxP (WT)_, 10 RI Cre (WT), and 14 βTRAF2 islet transplant recipients were tested. (B) Blood glucose and AUC were assessed in 8 TRAF2_loxP/loxP (WT), 4 RI Cre (WT), and 10 βTRAF2 islet transplant recipients after i.p. injection of d-glucose at day 11 after transplant. Data are representative of three independent mouse cohorts tested. *, P < 0.05. (C) Insulin levels and AUC were assessed in 6 TRAF2_loxP/loxP (WT), 4 RI Cre (WT), and 10 βTRAF2 islet transplant recipients after i.v. injection of d-glucose at day 21 after transplant. Data are representative of three independent mouse cohorts tested. *, P < 0.05. (D) H&E staining and insulin immunohistochemistry of WT and βTRAF2 islet grafts are shown. Graft β cell area was determined for three WT and three βTRAF2 islet grafts by quantification of insulin-positive area in continuous serial graft sections. A representative image for each condition is shown. Boxed insets represent magnified area. Differences in graft area are not significant (P > 0.05). Bar, 100 µm. (E) In vitro GSIS in 2, 11, and 20 mM d-glucose and in KCl conditions in WT and βTRAF2 mouse islets was measured. Data are mean and SEM derived from six independent islet isolates for each group, and are representative of two independent experiments. **, P < 0.01. All data are represented as mean ± SEM; p-values were determined using Student’s t test.