Practical Journal of Organ Transplantation(Electronic Version) ›› 2022, Vol. 10 ›› Issue (5): 436-439.DOI: 10.3969/j.issn.2095-5332.2022.05.012

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Insulin therapy potentiates the effect of PDX-1 to induce pancreatic islet β cell regeneration 

Wei Lingling,Zhang Lijie,Yang Longyan,Zhao Dong.   

  1. Beijing Key Laboratory of Diabetes Prevention and Research, Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing 101149China. 

  • Online:2022-09-20 Published:2022-09-20

胰岛素治疗在再生中的作用 PDX-1 诱导胰岛 β 细胞 

魏玲玲,张丽洁,杨龙艳,赵冬   

  1. 首都医科大学附属北京潞河医院内分泌代谢与免疫性疾病中心,糖尿病防治研究北京市重点实验室,北京 101149

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 injection200 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 ,