Acarbose ameliorates spontaneous type‑2 diabetes in db/db mice by inhibiting PDX‑1 methylation.
Acarbose ameliorates spontaneous type‑2 diabetes in db/db mice by inhibiting PDX‑1 methylation.
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DOI：
10.3892/mmr.2020.11710
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发表时间：
2021-01
影响因子：
3.4
通讯作者：
Mou X
中科院分区：
文献类型：
--
作者：
Zhou D;Chen L;Mou X
胰腺和十二指肠同源盒基因（PDX）-1是一个在胰腺发育和功能中起重要作用的基因。2型糖尿病（T2 DM）是一种与胰岛素抵抗和胰岛β细胞功能受损相关的代谢性疾病。有证据表明PDX-1的甲基化在T2 DM的发展中起作用。阿卡波糖是一种α-葡萄糖苷酶抑制剂，可有效延缓机体对葡萄糖的吸收。本研究的目的是检测阿卡波糖对自发性2型糖尿病db/db小鼠胰岛β细胞中PDX-1甲基化的影响。通过测量摄食量、体重、糖化血红蛋白（HbA 1c）、胰高血糖素、血清总胆固醇和甘油三酯水平以及空腹血糖（FBG），评估阿卡波糖对这些小鼠中葡萄糖和脂质代谢的影响。还使用腹膜内葡萄糖耐量和胰岛素耐量试验分析血糖水平。免疫组化法观察阿卡波糖对胰腺病理改变的影响。此外，使用BrdU测定来分析细胞增殖。最后，使用甲基化特异性PCR和蛋白质印迹分析在小鼠中评估阿卡波糖对PDX-1甲基化的影响。在本研究中，与正常组相比，阿卡波糖组的体重显著增加。与正常组相比，T2 DM组的HbA 1c和胰高血糖素水平显著升高，而阿卡波糖治疗组的HbA 1c和胰高血糖素水平显著降低。此外，与T2 DM小鼠相比，阿卡波糖组的FBG水平显著降低。阿卡波糖也促进细胞增殖，与未经治疗的T2 DM小鼠相比。此外，与T2 DM组相比，阿卡波糖组的PDX-1甲基化和细胞质表达水平均下调。以上结果提示，阿卡波糖可促进糖尿病小鼠胰岛β细胞增殖，抑制胰岛β细胞PDX-1甲基化。因此，阿卡波糖可能为T2 DM的治疗提供一种新的策略。
Pancreatic and duodenal homeobox (PDX)-1 is a gene that plays an important role in pancreatic development and function. Type-2 diabetes mellitus (T2DM) is a metabolic disease associated with insulin resistance and impaired islet β-cell function. There is evidence that methylation of PDX-1 plays a role in the development of T2DM. Acarbose is an α-glucosidase inhibitor that can effectively delay the absorption of glucose by the body. The aim of the present study was to examine the effect of acarbose on PDX-1 methylation in islet β-cells in spontaneous type-2 diabetic db/db mice. The effect of acarbose on glucose and lipid metabolism in these mice was assessed by measuring food intake, body weight, glycated hemoglobin (HbA1c), glucagon, serum total cholesterol and triglyceride levels, and fasting blood glucose (FBG). Blood glucose levels were also analyzed using intraperitoneal glucose tolerance and insulin tolerance tests. Immunohistochemistry was used to evaluate the effect of acarbose on pathological changes in the pancreas. Moreover, a BrdU assay was used to analyze cell proliferation. Lastly, the effect of acarbose on PDX-1 methylation was evaluated in mice using methylation-specific PCR and western blot analysis. In the present study, body weight significantly increased in the acarbose group, compared to the normal group. The levels of HbA1c and glucagon in the T2DM group significantly increased, compared with the normal group, but significantly decreased in acarbose-treated mice. Moreover, FBG levels significantly decreased in the acarbose groups compared with T2DM mice. Acarbose also promoted cell proliferation, compared with untreated T2DM mice. In addition, PDX-1 methylation and cytoplasmic expression levels were both downregulated in the acarbose group, compared with the T2DM group. In conclusion, these results suggested that acarbose could promote the proliferation of islet β-cells and inhibit PDX-1 methylation in islet β cells from diabetic mice. Thus, acarbose may provide a new strategy to treat T2DM.