Glucose-responsive expression of the human insulin promoter in HepG2 human hepatoma cells.
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.
Burkhardt
Brant R
BR
Department of Pathology, University of Florida, Gainesville, Florida 32610, USA.
Loiler
Scott A
SA
Anderson
Jo Anne
JA
Kilberg
Michael S
MS
Crawford
James M
JM
Flotte
Terence R
TR
Goudy
Kevin S
KS
Ellis
Tamir M
TM
Atkinson
Mark
M
D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D017931:DNA Primers; D006597:Fructose-Bisphosphatase / Q000235:genetics; D005947:Glucose / Q000502:physiology*; D005952:Glucose-6-Phosphatase / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D011401:Promoter Regions, Genetic; D051381:Rats; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D007328:Insulin; D006597:Fructose-Bisphosphatase; D005952:Glucose-6-Phosphatase; D005947:Glucose