胰岛素治疗在PDX-1诱导胰岛β细胞再生中的作用  

Insulin therapy potentiates the effect of PDX-1 to induce pancreatic isletβcell regeneration

作　　者：魏玲玲 张丽洁 杨龙艳 赵冬[1] Wei Lingling;Zhang Lijie;Yang Longyan;Zhao Dong(Beijing Key Laboratory of Diabetes Prevention and Research,Center for Endocrine Metabolism and Immune Diseases,Beijing Luhe Hospital,Capital Medical University,Beijing 101149,China.)

机构地区：[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

出　　处：《实用器官移植电子杂志》2022年第5期439-442,共4页Practical Journal of Organ Transplantation(Electronic Version)

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。Objective The addition of insulin therapy to transient expression of the transcription factor(pancreatic and duodenal homeobox gene 1,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 with either 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 isletβcells 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.

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 

分 类 号：R587.1[医药卫生—内分泌]