Figure 5. UCn2 gene transfer increases glucose disposal in db/db mice.

Mice (db/db) received i.v. AAV8.UCn2 (5 × 10¹¹ gc) or saline and were studied 4 weeks after gene transfer. (A) UCn2 expression. UCn2 gene transfer was associated with a > 450-fold increase in liver mRNA expression 4 weeks after gene transfer (P = 0.0016). (B) Fasting glucose. Blood was sampled after a 12-hr fast in 5 male and 6 female db/db mice. One day after gene transfer (Day 1), mice that had received saline (db/db; n = 11) and UCn2 gene transfer (+UC, n = 11) had similar levels of hyperglycemia. However, 4 weeks later (Week 4), mice that had received UCn2 gene transfer had a 42% reduction in blood glucose (P = 0.0001). (C) Glucose tolerance test in db/db mice. Mice (db/db) received i.v. AAV8.UCn2 (+UCn2; 5 × 10¹¹ gc, n = 5) or saline (db/db, n = 5). One month later, fasted mice (12 hr) received glucose (2 mg/g, i.p.), and glucose levels were measured (C). The AUC was reduced by 57% (P = 0.003). These results indicate that UCn2 gene transfer promotes glucose disposal and protects against hyperglycemia, confirming its efficacy in a second model of insulin resistance.