New strategies are needed in the treatment of patients with Type I diabetes. The best way to develop new strategies is to understand in greater detail all aspects of the glucose sensitive insulin release mechanism of the pancreatic beta cell. Two enzymes in this pathway that may be important are the mitochondrial and cytoplasmic forms of glycerol- 3-phosphate dehydrogenase, ie, the glycerol phosphate shuttle. By better defining the role of these enzymes and by developing methods to alter their expression, the insulin response might potentially be improved. A replication defective recombinant adenovirus containing these genes will be constructed and will be used to introduce these genes into a glucose sensitive insulin secreting cell line (beta HC cells) in vitro. Glucose perfusion studies will characterize the role of these enzymes in this setting. Eventually, these genes might be introduced into islets in attempts to improve their function during transplantation.
| McClane, S J; Chirmule, N; Burke, C V et al. (1997) Characterization of the immune response after local delivery of recombinant adenovirus in murine pancreas and successful strategies for readministration. Hum Gene Ther 8:2207-16 |
| McClane, S J; Hamilton, T E; Burke, C V et al. (1997) Functional consequences of adenovirus-mediated murine pancreatic gene transfer. Hum Gene Ther 8:739-46 |
