Intra-arterial targeted islet-specific expression of Sirt1 protects β 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 (C.T.). The results showed that >95% of islets and about 60% of β cells within the pancreatic body and tail could be labeled 3 days after surgery. α-Cell labeling was not as efficient, whereas labeling of nonendocrine 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 (STZ)-induced type 1 diabetic model. The results demonstrated that overexpression of Sirtuin in STZ-treated mice reduced the level of β-cell death and extent of glucose intolerance. This study reports 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.
Tang
Mi-mi
MM
Multidisciplinary Research Center, Shantou University, Shantou, China.
Zhu
Qin-e
QE
Fan
Wen-zhu
WZ
Zhang
Shui-li
SL
Li
Di-zheng
DZ
Liu
Li-zhong
LZ
Chen
Miao
M
Zhang
Mei
M
Zhou
Jing
J
Wei
Chi-ju
CJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D018149:Glucose Intolerance / Q000628:therapy; D049452:Green Fluorescent Proteins / Q000235:genetics; D007269:Injections, Intra-Arterial; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy / Q000379:methods; D010179:Pancreas / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D012235:Rhodamines; D056564:Sirtuin 1 / Q000096:biosynthesis* / Q000235:genetics; D013311:Streptozocin / Q000494:pharmacology*; D019076:Transgenes
D001786:Blood Glucose; D012235:Rhodamines; D049452:Green Fluorescent Proteins; D013311:Streptozocin; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1