Intra-Arterial Targeted Islet-Specific Expression Of Sirt1 Protects Beta Cells From Streptozotocin Induced Apoptosis In Mice

Gene therapy provides a promising approach to curing diabetes. However, an effective route for islet-specific targeting has yet to be established. Toward this end, the pancreatic blood circulation system in Balb/c mice was determined by the injection of rhodamine-containing beads. The efficiency of islet targeting was then measured by the injection of adenoviral vectors carrying a green fluorescence gene via the celiac trunk. The results showed that more than 95% of islets and about 60% of beta cells within the pancreatic body and tail could be labeled three days after surgery. Alpha cell labeling was not as efficient, while labeling of non-endocrine tissues was barely detectable. For proof of principle, adenoviral vectors carrying a Sirtuin transgene were injected similarly to test the islet protection effect in the streptozotocin-induced type 1 diabetic model. The results demonstrated that over-expression of Sirtuin in streptozotocin-treated mice reduced the level of beta cell death and extent of glucose intolerance. To our knowledge, this is the first report on efficient islet-specific targeting by using adenoviral injection. This procedure could be invaluable to the treatment of diabetes and the study of islet biology.