کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2197841 1550989 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Adeno-associated viral delivery of a metabolically regulated insulin transgene to hepatocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Adeno-associated viral delivery of a metabolically regulated insulin transgene to hepatocytes
چکیده انگلیسی

Transduction with a liver specific, metabolically responsive insulin transgene produces near-normal blood sugars in STZ-diabetic rats. To overcome the limited duration of hepatic transgene expression induced by E1A-deleted adenoviral vectors, we evaluated recombinant adeno-associated virus (rAAV2) for cell type specificity and glucose responsiveness in vitro. Co-infection of AAV2 containing the glucose responsive, liver-specific (GlRE)3BP-1 promoter with an empty adenovirus enhanced transduction efficiency, and shortened the duration of transgene expression in HepG2 hepatoma cells, but not primary hepatocytes. However, in the context of rAAV2, (GlRE)3BP-1 promoter activity remained confined to cells of hepatocyte lineage, and retained glucose responsiveness. While isolated infection with an insulin expressing rAAV2 failed to attenuate blood sugars in diabetic mice, adenoviral co-administration with the same rAAV2 induced transient, near-normal random blood sugars in a diabetic animal. We conclude that rAAV2 can induce metabolically responsive insulin secretion from hepatocytes in vitro and in vivo. However, alternative AAV serotypes will likely be required to efficiently deliver therapeutic genes to the liver for the treatment of diabetes mellitus.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Endocrinology - Volume 273, Issues 1–2, 15 July 2007, Pages 6–15
نویسندگان
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