(A) AAV8.UCn2 map. Initial studies in mice determined that AAV8.CBA.UCn2 is the optimal AAV serotype and promoter for the proposed studies resulting in a sustained increase in plasma UCn2 levels over 7 months (5). (B) Fasting glucose. Normal mice received i.v. AAV8.UCn2 (5 × 1011 gc, n = 8), saline (CON, n = 8), or AAV9.EGFP (5 × 1011 gc, n = 4) and standard chow for 3 weeks. A 24% reduction in fasting glucose was seen after AAV8.UCn2 gene transfer (P = 0.01). (C) AAV8.UCn2 dose-glucose response relationship. AAV8.UCn2 doses of 5 × 109 to 5 × 1011 gc produced 21%–33% reduction in fasting glucose levels in normal mice. We selected the highest dose (5 × 1011 gc) for studies conducted in insulin resistant mice. In all graphs, data are mean ±SEM; P values are from Student’s t test for unpaired data, 2 tails, unless stated otherwise.