Glucose-responsive expression of the human insulin promoter in HepG2 human hepatoma cells.

ABSTRACT

The concept of insulin production afforded by hepatic gene therapy retains promise as a potential therapy for type 1 diabetes, but the approach has been limited by the need for strict transgene regulation in response to fluctuating levels of both glucose and insulin. Furthermore, while hepatocytes contain various glucose-responsive elements, they lack the appropriate regulated secretory system necessary for insulin release, thereby necessitating the requirement for transcriptional regulation of hepatic insulin production under the direction of a glucose-responsive promoter. To address this, we have evaluated several glucose-responsive promoters that may be used successfully for hepatic insulin production via recombinant adeno-associated virus (rAAV) therapy. Our results suggest that the human insulin promoter represents a strong candidate as a robust, glucose-responsive promoter for regulated hepatic insulin production.