Glucose inducible insulin expression and methods of treating diabetes

摘要

The invention provides an isolated tissue specific glucose responsive promoter having a polymerase binding domain 3' to at least one tripartite transcription factor binding cis element having a hepatocyte nuclear factor-1 (HNF-1) element, a CAAT/enhancer binding protein (C/EBP) response element and a glucose-response element (GRE). The promoter can include a second or third tripartite transcription factor binding cis element. A host cell including the tissue specific glucose responsive promoter of the invention also are provided. Further provided is a method of treating or preventing diabetes. The method includes administering to an individual an effective amount of a viral particle having a vector comprising a tissue specific glucose responsive promoter comprising a polymerase binding domain 3' to at least one tripartite transcription factor binding cis element having a hepatocyte nuclear factor-1 (HNF-1) element, a CAAT/enhancer binding protein (C/EBP) response element and a glucose-response element (GRE) operationally linked to an insulin encoding nucleic acid, wherein expression of the insulin encoding nucleic acid is tissue specific and glucose responsive.