This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The primary aim of this study is the establishment of a model of induced type 1 diabetes in baboons through beta cell compromise with streptozotocin (STZ), with the subsequent recovery of insulin production through gene therapy by the delivery of a specific gene using micro-bubble technology and their subsequent selective destruction in the pancreas via ultrasound. This study will be conducted in six phases. . The first two phases will include animal selection and acclimation, followed by the induction of type 1 diabetes via STZ administration. Animals will then be allowed to recover and the development of hyperglycemia will be tracked. Once the animals are stabilized and hyperglycemia has been achieved the animals will receive an injection of the micro-bubbles containing the test gene followed by the destruction of the micro-bubbles in the pancreas via ultrasound. Animals will continue to have their glucose levels monitored at regular intervals to look for improvement in glucose regulation. At the end of the experimental period the animals will be euthanized and key tissues will be collected for histopathological analyses to confirm gene uptake in the pancreas.
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