Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/93011
標題: Deletion of the CPR gene prevent streptozotocin-induced hyperglycemia in mice
CPR 基因剔除可預防 streptozotocin 誘導小鼠高血糖症
作者: Tzu-Yi Hu
胡慈驛
關鍵字: β 細胞;糖尿病;高血症;活性氧化物;streptozotocin;β-cell;diabetes;hyperglycemia;reactive oxygen species;streptozotocin
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摘要: 
在正常生理的情況下,內源性的活性氧化物(reactive oxygen species, ROS)幫助維持生理平衡。在糖尿病的情況下,長期處於慢性的高血糖環境,會造成細胞產生 ROS 使得 β 細胞的氧化壓力上升,因此進而導致 β 細胞失去功能(β-celldysfunction)或細胞凋亡(apoptosis)。在我們實驗室的研究顯示,CPR 基因與氧化壓力的調節有關係,並利用 streptozotocin (STZ) 誘導小鼠胰島細胞內 ROS 的產生,發現 CPR 基因剔除小鼠可減弱 STZ 誘發小鼠胰島細胞氧化壓力。在本研究中,我們使用 CPR 基因剔除小鼠在 STZ 誘導胰島 β 細胞氧化壓力之下並研究胰島素分泌能力。CPR 蛋白質表現可在對照組野生型(wild-type, WT)小鼠胰臟中表現,但 CPR 基因剔除小鼠則沒有表現。我們研究發現利用多次低劑量不同濃度的 STZ(30 mg/kg 與 40 mg/kg)投予 CPR 基因剔除小鼠以及野生型小鼠,CPR 基因剔除小鼠顯血糖值濃度相較於野生型小鼠有顯著的較低;STZ 投予後28 天,小鼠接受葡萄糖耐受性試驗,CPR 基因剔除小鼠與野生型小鼠相比有較良好的葡萄糖耐受性,並且發現 CPR 基因剔除小鼠其血清中的胰島濃度也比較高。為了進一步了解CPR 在造成高血糖誘導氧化壓力扮演什麼角色,我們在in vitro 實驗,DHE (Dihydroethidium)染色顯示在 MIN6 細胞株(β -細胞株)處理高糖(30 mM)有明顯的 ROS 表現,然而 CPR 蛋白表現也在 MIN6 細胞株處理高糖 24 小時後有增加。根據這些結果可推測 CPR 可能與胰島 β 細胞細胞 ROS生成有關,可改善 STZ 所誘導的高血糖發生,因此 CPR 可能在未來作為治療糖尿病或高血症的指標之一。

In physiologic concentrations, endogenous reactive oxygen species (ROS) help to maintain homeostasis. In the case of diabetes mellitus (DM), chronic exposure to hyperglycemia leads to the generation of ROS, resulting in oxidative stress in β-cell, and therefore dysfunction or cell apoptosis ensues. In our former work, we found that CPR , associated with ROS regulation, knockout (CPR KO) mice has the ability to reduce streptozotocin(STZ)-induced ROS expression in islet cell. In this study, we investigated the role of the CPR in STZ-induced oxidative stress on β-cell and insulin secretion ability by using CPR KO mice. CPR was expressed in the pancreas of wild- type (WT) mice, but not in CPR KO mice. We observed that CPR KO mice showed a significant decrease in blood glucose concentration compare with WT mice after multiple doses of 30 or 40 mg/kg body weight STZ treatment. The intraperitoneal glucose tolerance tests (IPGTT) showed that the glucose clearance was significantly improved in the CPR KO mice than in the WT mice at 28 days after STZ treatment. The serum insulin levels were also higher in the CPR KO mice than in the WT mice at 28 days after STZ treatment. To clarify the role of CPR during hyperglycemia-induced oxidative stress, we performed in vitro experiments. DHE (Dihydroethidium) staining revealed that the level of ROS was significantly increase in MIN6 cell line (β-cell line) after treated with high glucose concentration (30mM), whereas CPR protein was increase expressed by western blot at 24 h. These results suggest that CPR may be involved in ROS synthesis in β-cell to ameliorate streptozotocin-induced hyperglycemia, and CPR would therefore be a good target for the treatment of hyperglycemia or diabetes mellitus.
URI: http://hdl.handle.net/11455/93011
其他識別: U0005-3005201514572700
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