Oligodeoxynucleotide IMT504 induces a marked recovery in a streptozotocin-induced model of diabetes in rats: correlation with an early increase in the expression of nestin and neurogenin 3 progenitor cell markers
Oligodeoxynucleotide IMT504 induces a marked recovery in a streptozotocin-induced model of diabetes in rats: correlation with an early increase in the expression of nestin and neurogenin 3 progenitor cell markers
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DOI：
10.1007/s00125-010-1694-z
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发表时间：
2010-06-01
期刊：
影响因子：
8.2
通讯作者：
Lux-Lantos, V. A.
中科院分区：
文献类型：
--
作者：
Bianchi, M. S.;Hernando-Insua, A.;Lux-Lantos, V. A.
IMT504是一种寡核苷酸，通过刺激祖细胞促进骨损伤和神经病理性疼痛模型的组织修复。在此，我们评价了IMT504对链脲佐菌素(STZ)诱导的大鼠糖尿病模型胰岛功能恢复的影响。雄性SD大鼠注射STZ(60 mg/kg，ip，第1天)或柠檬酸盐缓冲液(对照组)。第4天血糖控制在11~20 mm ol/L的动物，分别注射IMT504(生理盐水4 mg/只)或生理盐水(STZ-生理盐水)，连续10d。记录血糖、水和食物摄入量，持续33天。第30天进行腹膜糖耐量试验(IPGTTS)。在第35天，隔夜禁食的动物被处死，采集血液和胰腺样本进行激素和组织学研究。第二组STZ-IMT504大鼠与对照组和STZ-生理盐水大鼠一起，在IMT504治疗开始后连续两天血糖下降后被处死。用免疫组织化学方法检测胰腺组织中增殖细胞核抗原(PCNA)、巢蛋白和神经原蛋白3(NGN3)的表达。IMT504能显著改善STZ-IMT504大鼠第8天的血糖、食物和水的摄入量以及第30天的IPGTT。STZ-IMT504大鼠(第33天)胰岛数量和胰岛β细胞含量显著增加。此外，注射2-5次IMT504后，STZ-IMT504大鼠血糖下降，胰腺巢蛋白(主要是内皮细胞)、增殖细胞核抗原和NGN3的产生(在胰岛)增加。IMT504诱导STZ诱导的糖尿病明显恢复，这与早期产生前体细胞标志物如巢蛋白和NGN3有关。
IMT504 is an oligonucleotide that promotes tissue repair in bone injury and neuropathic pain models by stimulating progenitor cells. Here we evaluated the effect of IMT504 on the recovery of islet function in a streptozotocin (STZ)-induced model of diabetes in the rat.Male Sprague-Dawley rats were injected with STZ (60 mg/kg, i.p., day 1) or citrate buffer (Control). Animals with glycaemia between 11 and 20 mmol/l on day 4 were injected with IMT504 (4 mg/animal in saline, s.c., STZ-IMT504) or with saline (STZ-Saline) for 10 days. Glycaemia and water and food intake were recorded for 33 days. Intraperitoneal glucose tolerance tests (IPGTTs) were performed on day 30. On day 35, overnight-fasted animals were killed and blood samples and pancreases collected for hormonal and histological studies. A second group of STZ-IMT504 rats was killed, together with Control and STZ-Saline rats, after two consecutive days of blood glucose decreases after the beginning of IMT504 treatment. Pancreases were collected and proliferating cell nuclear antigen (PCNA), nestin and neurogenin 3 (NGN3) detected by immunohistochemistry.IMT504 greatly improved blood glucose and food and water intakes in STZ-IMT504 rats by day 8, as well as IPGTTs on day 30. Significant increases in islet number and beta cell content were observed in STZ-IMT504 rats (day 33). Furthermore, after two to five IMT504 injections, blood glucose decreased, and an increase in pancreatic nestin (mainly in endothelial cells), PCNA and NGN3 production (in islets) was observed in STZ-IMT504 rats.IMT504 induced a marked recovery of STZ-induced diabetes that correlated with early production of progenitor cell markers, such as nestin and NGN3.