Vildagliptin preserves the mass and function of pancreatic β cells via the developmental regulation and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes.
Vildagliptin preserves the mass and function of pancreatic β cells via the developmental regulation and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes.
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DOI：
10.1111/dom.12005
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发表时间：
2013-02
期刊：
影响因子：
--
通讯作者：
Kaku K
中科院分区：
文献类型：
--
作者：
Hamamoto S;Kanda Y;Shimoda M;Tatsumi F;Kohara K;Tawaramoto K;Hashiramoto M;Kaku K
我们研究了维达戈肽保护胰腺β细胞质量和功能的分子机制。在8周龄的雄性KK-Ay-TaJcl（KK-Ay）和C57 BL/6 JJcl（B6）小鼠中研究了胰岛的形态学、生物化学和基因表达谱，这些小鼠接受了4周的维格鲁肽或溶媒。体重，食物摄入量，空腹血糖，血浆胰岛素和活性胰高血糖素样肽-1在这两种小鼠中与vildagelatin治疗无变化。在用维格鲁肽治疗的KK-Ay小鼠中，升高的血浆甘油三酯（TG）水平和胰岛TG含量降低，胰岛素敏感性显著改善，并且葡萄糖耐量随着血浆胰岛素水平的升高而改善。此外，在两种菌株中，维达鲁肽增加葡萄糖刺激的胰岛素分泌、胰岛胰岛素含量和胰腺β细胞质量。在KK-Ay小鼠中，通过vildagelide，参与细胞分化/增殖的基因的表达在两种菌株中上调，与凋亡、内质网应激和脂质合成相关的基因的表达降低，与抗凋亡和抗氧化应激相关的基因的表达上调。形态学结果与基因表达谱一致。在糖尿病小鼠中，维达西汀不仅通过直接影响细胞动力学，而且通过间接减少细胞凋亡、氧化应激和内质网应激来增加β细胞质量。
We investigated the molecular mechanisms by which vildagliptin preserved pancreatic β cell mass and function. Morphological, biochemical and gene expression profiles of the pancreatic islets were investigated in male KK-Ay-TaJcl(KK-Ay) and C57BL/6JJcl (B6) mice aged 8 weeks which received either vildagliptin or a vehicle for 4 weeks. Body weight, food intake, fasting blood glucose, plasma insulin and active glucagon-like peptide-1 were unchanged with vildagliptin treatment in both mice. In KK-Ay mice treated with vildagliptin, increased plasma triglyceride (TG) level and islet TG content were decreased, insulin sensitivity significantly improved, and the glucose tolerance ameliorated with increases in plasma insulin levels. Furthermore, vildagliptin increased glucose-stimulated insulin secretion, islet insulin content and pancreatic β cell mass in both strains. By vildagliptin, the expression of genes involved in cell differentiation/proliferation was upregulated in both strains, those related to apoptosis, endoplasmic reticulum stress and lipid synthesis was decreased and those related to anti-apoptosis and anti-oxidative stress was upregulated, in KK-Ay mice. The morphological results were consistent with the gene expression profiles. Vildagliptin increases β cell mass by not only directly affecting cell kinetics but also by indirectly reducing cell apoptosis, oxidative stress and endoplasmic reticulum stress in diabetic mice.
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影响因子：
3.5
作者：
HAMMONDS, P;SCHOFIELD, PN;GRAY, DWR
通讯作者：
GRAY, DWR
影响因子：
5.8
作者：
Reimer, MK;Holst, JJ;Ahrén, B
通讯作者：
Ahrén, B
影响因子：
15.9
作者：
NAUCK, MA;HEIMESAAT, MM;CREUTZFELDT, W
通讯作者：
CREUTZFELDT, W
影响因子：
8.2
作者：
Shimoda, M.;Kanda, Y.;Hamamoto, S.;Tawaramoto, K.;Hashiramoto, M.;Matsuki, M.;Kaku, K.
通讯作者：
Kaku, K.
影响因子：
8.2
作者：
Buteau, J;Roduit, R;Prentki, M
通讯作者：
Prentki, M