Effects of dapagliflozin and/or insulin glargine on beta cell mass and hepatic steatosis in db/db mice
Effects of dapagliflozin and/or insulin glargine on beta cell mass and hepatic steatosis in db/db mice
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DOI：
10.1016/j.metabol.2019.06.006
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发表时间：
2019-09-01
影响因子：
9.8
通讯作者：
Atsumi, Tatsuya
中科院分区：
文献类型：
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作者：
Omori, Kazuno;Nakamura, Akinobu;Atsumi, Tatsuya
目的：方法：将6周龄的db/db小鼠分配到四个组中的一个：未处理的（安慰剂）、用达格列净（达帕）处理的、用甘精胰岛素（Gla）处理的、或用达格列净和甘精胰岛素（达帕+Gla）处理的。治疗8周后，我们确定葡萄糖耐量，β细胞质量，肝脂质含量和基因expression.Results：葡萄糖耐量显着改善在三个治疗组相比，安慰剂组相同程度。免疫组织化学分析显示，与安慰剂组相比，达帕和达帕+Gla组显著维持了胰腺β细胞质量，但Gla组没有（安慰剂组2.25 +/- 1.44 mg，达帕5.01 +/- 1.63 mg，Gla 3.79 +/- 0.96 mg，达帕+Gla 5.19 +/- 1.78 mg）。然而，与其他三个组相比，Gla组的肝脏甘油三酯含量显著升高（安慰剂组24.1 +/- 11.5 mg，达帕组30.6 +/- 12.9 mg，Gla组128 +/- 49.7 mg，达帕+Gla组54.4 +/- 14.1 mg/g肝脏）。与脂肪酸合成和脂质储存相关的基因的表达水平显着上调Gla group.Conclusions：我们的研究结果表明，β细胞群持续和肝脂肪变性被阻止，8周后，无论是达格列净或达格列净加甘精胰岛素治疗，但不是单独用甘精胰岛素，在db/db小鼠。(C)2019爱思唯尔公司All rights reserved.
Objective: To explore the beneficial effects of dapagliflozin and/or insulin glargine on the pancreatic beta cell mass and hepatic steatosis in db/db mice.Methods: Six-week-old db/db mice were assigned to one of four groups: untreated (Placebo), treated with dapagliflozin (Dapa), treated with insulin glargine (Gla), or treated with dapagliflozin and insulin glargine (Dapa+Gla). After 8 weeks of treatment, we determined glucose tolerance, beta cell mass, hepatic lipid content and gene expression.Results: Glucose tolerance was significantly ameliorated in the three treated groups to the same degree compared with the Placebo group. Immunohistochemical analysis revealed that the pancreatic beta cell mass was significantly maintained in the Dapa and Dapa+Gla groups, but not in the Gla group, compared with the Placebo group (Placebo 2.25 +/- 1.44 mg, Dapa 5.01 +/- 1.63 mg, Gla 3.79 +/- 0.96 mg, Dapa+Gla 5.19 +/- 1.78 mg). However, the triglyceride content of the liver was markedly elevated in the Gla group compared with that in the other three groups (Placebo 24.1 +/- 11.5 mg, Dapa 30.6 +/- 12.9 mg, Gla 128 +/- 49.7 mg, Dapa+Gla 54.4 +/- 14.1 mg per gram liver). The expression levels of genes related to fatty acid synthesis and lipid storage were significantly upregulated in the Gla group.Conclusions: Our results showed that beta cell mass was sustained and hepatic steatosis was prevented, after 8weeks of treatment with either dapagliflozin or dapagliflozin plus insulin glargine, but not with insulin glargine alone, in db/db mice. (C) 2019 Elsevier Inc. All rights reserved.