Glucose-Responsive Expression of the Human Insulin Promoter in HepG2 Human Hepatoma Cells

• Published in: Annals of the New York Academy of Sciences Vol. 1005; no. 1; pp. 237 - 241
• Main Authors: BURKHARDT, BRANT R., LOILER, SCOTT A., ANDERSON, JO ANNE, KILBERG, MICHAEL S., CRAWFORD, JAMES M., FLOTTE, TERENCE R., GOUDY, KEVIN S., ELLIS, TAMIR M., ATKINSON, MARK
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2003
• Subjects: Animals; Base Sequence; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; diabetes; DNA Primers; Fructose-Bisphosphatase - genetics; Glucose - physiology; Glucose-6-Phosphatase - genetics; Humans; insulin; Insulin - genetics; Liver Neoplasms, Experimental - metabolism; Liver Neoplasms, Experimental - pathology; Mice; Mice, Inbred NOD; promoter; Promoter Regions, Genetic; Rats; transfection; Tumor Cells, Cultured
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1196/annals.1288.035

: 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.