Adeno-associated virus-mediated pancreatic and duodenal homeobox gene 1 delivery induced insulin-producing cells in livers of diabetic rats

Abstract

Abstract: AIM:Pancreatic and duodenal homeobox gene 1(pdx-1) is a crucial transcription factor in pancreatic islet development and differentiation. This study was conducted to evaluate whether pdx-1 delivered by adenoassociated virus (AAV) could induce liver cells to differentiate into insulin-producing cells in diabetic rats and thus provide more information for cell replacement therapy for diabetes.METHODS: Recombinant AAV vector was employed to deliver pdx-1to STZ-induced diabetic rats via portal vein (4 ×10¹¹). Blood glucose and body weight were monitored. Gene expression of pdx-1 and insulin were determined by RT-PCR and immunocytotochemistry (ICC) at the 6th week after the injection.RESULTS: AAV-pdx-1 group showed obvious gene expression of pdx-1 and insulin by RT-PCR analysis and the presence of more insulin-positive cells by ICC. Hyperglycemia was partially ameliorated and body weight was also increased in AAV-pdx-1 treated diabetic rats, though still significantly different from those in the non-diabetic group.CONCLUSION:The data indicate that AAV-pdx-1 can induce more rat liver cells into insulin-producing cells in vivo, thereby ameliorate hyperglycemia. Further experiments are needed to explore which subpopulation of liver cells responds to this development shift and the mechanism of this development shift induced by pdx-1 in order to improve the differentiation efficiency.

Key words: adeno-associated virus, pancreatic and duodenal homeobox gene 1, insulin, diabetes, hyperglycemia

CLC Number:

R966

LI Hua, LI Xin-yan, XU Rui-an. Adeno-associated virus-mediated pancreatic and duodenal homeobox gene 1 delivery induced insulin-producing cells in livers of diabetic rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(6): 614-619.

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