abstract |
Hepatocytes transfected with a replication deficient adenovirus vector containing a gene cassette expressing the proinsulin gene in response to physiological levels of glucose provide novel beta islet replacement cells. The cassette comprises the structural gene for human proinsulin genetically altered to make it cleavable to active insulin, a promoter operably linked to the proinsulin gene, and a glucose regulatory response module located 5' to the promoter. Synthesis of proinsulin mRNA is ablated at less than 5mM glucose, and peaks at about 15 mM. |