Exendin-4通过上调pdx-1 mRNA表达促进STZ造模小鼠β细胞增生  

Exendin-4 stimulates β-cell proliferation by up-regulating pdx-1 mRNA in STZ-treated mice

作　　者：朱敏[1] 史虹莉[2] 方京冲[2] 施建英[3] 黄葵香[2] 

机构地区：[1]复旦大学附属华山医院老年科,上海200040 [2]复旦大学附属华山医院内分泌科,上海200040 [3]复旦大学医学院病理科

出　　处：《中华内分泌代谢杂志》2005年第6期557-560,共4页Chinese Journal of Endocrinology and Metabolism

摘　　要：目的观察腹腔内注射exendin-4对链脲佐菌素(STZ)造模小鼠的血糖、胰岛数目和pdx-1表达的影响.方法C57BL/6小鼠30只被分成3组:注射用水组、STZ 50 mg/kg+注射用水组和STZ 50mg/kg+exendin-4 0.1μg/g体重组.实验第1～10 d每日腹腔内注射注射用水或exendin-4,实验第3～7 d注射STZ.检测exendin-4注射期间和停药后血糖水平,停药后进行腹腔葡萄糖耐量试验(IPGTT)、胰腺胰岛计数和RT-PCR检测转录因子pdx-1的表达.结果STZ造模小鼠连续exendin-4注射期间平均血糖和注射用水组差异无统计学意义[(6.12±0.37vs6.21±0.41)mmol/L,P＞0.05];而与未注射exendin-4的STZ小鼠组比较血糖明显降低[(6.12±0.37vs9.59±1.08)nmol/L,P＜0.05];exendin-4停药后2周内的STZ+exendin-4组的平均血糖仍较STZ+注射用水组明显降低[(13.02±1.96vs18.55±3.14)mmol/L,P＜0.05].IPGTT显示STZ+exendin-4组的糖耐量较STZ+注射用水组明显改善,胰腺胰岛计数STZ+exendin-4组较STZ+注射用水组增加了近1倍,转录因子pdx-1的表达也明显上调(P＜0.05).结论Exendin-4对STZ造模小鼠的血糖不仅具有短期控制作用,而且停药后仍有一定的维持作用.Exendin-4改善了STZ造模小鼠的糖耐量,上调了pdx-1的表达,促进了胰岛的增生.Objective To observe the effects of exendin-4 on blood glucose level, number of islets and expression of pdx-1 in streptozotocin （STZ）-treated mice. Methods Thirty C57BL/6 mice were divided into 3 groups： control group （vehicle） , STZ group （STZ 50 mg/kg ＋ vehicle） and STZ ＋ exendin 4 group （ STZ 50 mg,/kg ＋ exendin-4 0.1 μg,/g weight）. Mice were intraperitoneally injected with exendin-4 or vehicle daily for 10 days. From day 3 to day 7, some of the mice were injected with STZ. Blood glucose level was tested during 10 days of injection and two weeks after injection. On day 30, intraperitoneal glucose tolerance test （IPGTT） was performed and the number of islets was counted and the gene expression of pdx-1 was detected by RT-PCR. Results The average blood glucose level in STZ ＋ exendin-4 group [ （6. 12 ± 0. 37） mmol/L] showed no significant difference from that of control group [ （6.21 ± 0.41 ） mmol/L, P 〉 0.05 ] , but was lower than that of STZ group [ （9.59±1.08）mmol/L, P 〈0.05]. During the two weeks after the cessation of exendin-4 injection, the blood glucose level in STZ ＋ exendin-4 group was still lower than that of STZ group [ （ 13.02 ± 1.96 vs 18.55 ±3.14 ） mmol/L, P 〈 0. 05 ]. As compared with STZ group, STZ ＋ exendin-4 group showed improvement in glucose tolerance, increment of islet number （ by 100% ） , and up-regulation of pdx-1 expression. Conclusion Exendin-4 exhibits a brief as well as long term benefit in STZ treated mice. It improves glucose tolerance, increases number of islets and up-regulates expression of pdx-1 mRNA.

关 键 词：胰高血糖索样肽1 EXENDIN-4 糖尿病 

分 类 号：R587.1[医药卫生—内分泌]