Glucose-responsive artificial promoter-mediated insulin gene transfer improves glucose control in diabetic mice

Figure 1 rAd-SP-rINSfur administration reduces high blood glucose levels to normal physiological range in Lepr^db/db mice. A: Schematic diagram of adenoviral construct expressing furin cleavable insulin gene under the control of synthetic promoter. The synthetic promoter is composed of nine transcription factor binding elements upstream of pyruvate kinase basal promoter (L-PK). A furin-cleavable site was introduced at the junction of the B-chain and C-peptide; B: Blood glucose levels; C: Body weights of Lepr^db/db mice treated with rAd-CMV-βgal or rAd-SP-rINSfur. Viruses were injected into experimental animals at 12 wk of age with a dose of 3 × 10¹⁰ viral particles, and blood glucose levels and body weights were monitored. Blood glucose levels and body weights were measured between 2-4 pm during the day, and food and water were given ad libitum during the experiments. All values are mean ± SE. Day 0 indicates the day of viral injection. HNF-1: Hepatocyte nuclear factor-1; C/EBP: CCAAT enhancer binding protein; GlRE: Glucose responsive elements; HNF-4: Hepatocyte nuclear factor-4.