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 ,

摘要：

目的 验证胰岛素治疗联合瞬时表达转录因子（胰腺十二指肠同源盒因子 -1，PDX-1） 可以使糖尿病小鼠胰腺的胰岛再生。方法 腹腔注射链脲佐菌素（Streptozotocin，STZ）（200 mg/kg）诱导小鼠糖尿病（BG ＞ 16.7 mmol/L）。 然后通过胰腺内注射编码 PDX-1（Ad-PDX-1）或 LacZ （Ad-LacZ）对照的腺病毒载体（1×109 pfu）进行基因转染，随后每天注射胰岛素，并进行体重、血糖和胰腺组织学检测。 结果 胰岛素治疗逐渐降低了 Ad-PDX-1 组的血糖水平，在 2 ~ 3 周内血糖降为正常（BG ＜ 11.1 mmol/L） 并脱离胰岛素。然而，在没有胰岛素的情况下，未观察到明显的效果。 Ad-LacZ 对照组的动物无论是否联合胰岛素治疗，在整个 30 d 的研究过程中持续高血糖。组织学分析表明，在用胰岛素和 Ad-PDX-1 处理的小鼠胰腺中，诱导了新的胰岛再生，且仅由分泌胰岛素的细胞组成，而在对照中没有或很少观察到胰岛素阳性细胞。 结论 瞬时表达 PDX-1 联合胰岛素治疗可有效诱导糖尿病小鼠胰腺中功能性胰岛 β 细胞再生，形成新的胰岛，逆转糖尿病。 这种方法可能会是治疗糖尿病的一种新策略。 

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 ,