Figure 4. UCn2 gene transfer in HFD-induced insulin resistance in CRHR2-deleted mice.

(A) Plasma UCn2 in CRHR2-deleted mice. First, we confirmed that i.v. AAV8.UCn2 (5 × 10¹¹ gc, i.v.) was associated with increased plasma UCn2 levels in CRHR2-deleted (KO) HFD-fed mice. Plasma UCn2 peptide was measured in pooled plasma (4 animals per group). High plasma levels of UCn2 were detected, in amounts similar to what we found in normal mice (5). (B) Glucose tolerance test 17 weeks after HFD, UCn2 gene transfer at 8 weeks. Fasted CRHR2-deleted mice received glucose (2 mg/g, i.p.), and glucose was measured sequentially for 120 min. There was no group difference in blood glucose levels (P = 0.21, AUC), indicating that UCn2’s cognate receptor, CRHR2, is required for UCn2 to increase glucose disposal rate. Contrast these data to those shown in Figure 2A, where a pronounced glucose lowering effect of UCn2 gene transfer is observed.