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Glucose‐Responsive Expression of the Human Insulin Promoter in HepG2 Human Hepatoma Cells
Author(s) -
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
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1288.035
Subject(s) - insulin , transgene , genetic enhancement , promoter , human insulin , recombinant dna , biology , diabetes mellitus , endocrinology , medicine , gene , gene expression , chemistry , biochemistry
A bstract : 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.