关键词:

胰岛素治疗 ；胰岛 β 细胞 ；再生 ；转录因子 ；胰腺十二指肠同源盒因子 -1 ,

Abstract:

Objective The addition of insulin therapy to transient expression of the transcription factor（pancreatic and duodenal homeobox gene1，PDX-1） may enable islet regeneration in the pancreas of diabetic mice. Methods Diabetes was induced in C57BL/6J mice（BG ＞ 16.7 mmol/L） by streptozotocin intraperitoneal injection（200 mg/kg）. Gene transfer was then performed by intra-pancreatic injection of an adenoviral vector （1×109 pfu）encoded witheither PDX-1（Ad-PDX-1） or LacZ （Ad-LacZ） control， followed by daily insulin administration. Body weight， blood glucose，and pancreas histology were monitored. Results Our results showed that insulin administration gradually decreased blood glucose level in Ad-Pdx1 group， which became euglycemic （BG ＜ 11.1 mmol/L） and insulin-independent in about two to three weeks. Without insulin， however, no obvious effect was observed. The animals in the Ad-LacZ control group （with or without insulin therapy）remained hyperglycemic throughout the 30 days study course. Histological analysis showed that newly formed islets consisting solely of insulin-producing cells were induced in the pancreas of the mice treated with both insulin and Ad-PDX-1, while no or very few insulin positive cells were observed in control. Conclusion Transient expression of PDX-1 combined with insulin treatment effectively induced the regeneration of functional islet β cells in the pancreas of the diabetic mice， forming new islet and reversing diabetes. This approach may prove to be a novel strategy for the treatment of diabetes.

Key words:

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Insulin therapy ； , Pancreatic islet β , cell ； , Regeneration ； , Transcription factor ； , Pancreatic and duodenal homeobox gene-1 ,