The human glucagon-like peptide-1 analogue liraglutide preserves pancreatic beta cells via regulation of cell kinetics and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes.
The human glucagon-like peptide-1 analogue liraglutide preserves pancreatic beta cells via regulation of cell kinetics and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes.
复制标题
DOI：
10.1007/s00125-011-2069-9
复制
发表时间：
2011-05
期刊：
影响因子：
8.2
通讯作者：
Kaku, K.
中科院分区：
文献类型：
--
作者：
Shimoda, M.;Kanda, Y.;Hamamoto, S.;Tawaramoto, K.;Hashiramoto, M.;Matsuki, M.;Kaku, K.
关键词：
我们研究了人胰高血糖素样肽 1 类似物利拉鲁肽保护糖尿病 db/db 小鼠胰腺 β 细胞的分子机制。 10 周龄的雄性 db/db 和 m/m 小鼠接受利拉鲁肽或载体治疗 2 天或 2 周。除了胰岛的形态学和生化分析之外，还通过激光捕获显微切割和实时 RT-PCR 研究了胰岛核心区域的基因表达谱。利拉鲁肽治疗 2 周改善了 db/db 小鼠的代谢变量和胰岛素敏感性。利拉鲁肽还增加了两种小鼠品系中葡萄糖刺激的胰岛素分泌（GSIS）和胰岛胰岛素含量，并降低了 db/db 小鼠中的三酰甘油含量。两种小鼠品系中涉及细胞分化和增殖的基因表达均受到利拉鲁肽的调节，在db/db小鼠中，利拉鲁肽下调了涉及促凋亡、内质网（ER）应激和脂质合成的基因，并上调了与抗凋亡和抗氧化应激相关的基因。在 2 天的实验中，利拉鲁肽略微改善了 db/db 小鼠的代谢变量，但 GSIS、胰岛素和三酰甘油含量未受影响。在db/db小鼠中，利拉鲁肽增加与细胞分化、增殖和抗凋亡相关的基因表达，并抑制与促凋亡相关的基因表达；它对与氧化应激或内质网应激相关的基因没有影响。 db/db小鼠胰岛细胞增殖、细胞凋亡和氧化应激的形态测量结果与基因表达分析结果一致。利拉鲁肽不仅通过直接调节细胞动力学，而且通过抑制氧化和内质网应激（继发于糖脂毒性的改善）来增加β细胞质量。
We investigated the molecular mechanism by which the human glucagon-like peptide-1 analogue liraglutide preserves pancreatic beta cells in diabetic db/db mice. Male db/db and m/m mice aged 10 weeks received liraglutide or vehicle for 2 days or 2 weeks. In addition to morphological and biochemical analysis of pancreatic islets, gene expression profiles in the islet core area were investigated by laser capture microdissection and real-time RT-PCR. Liraglutide treatment for 2 weeks improved metabolic variables and insulin sensitivity in db/db mice. Liraglutide also increased glucose-stimulated insulin secretion (GSIS) and islet insulin content in both mouse strains and reduced triacylglycerol content in db/db mice. Expression of genes involved in cell differentiation and proliferation in both mouse strains was regulated by liraglutide, which, in db/db mice, downregulated genes involved in pro-apoptosis, endoplasmic reticulum (ER) stress and lipid synthesis, and upregulated genes related to anti-apoptosis and anti-oxidative stress. In the 2 day experiment, liraglutide slightly improved metabolic variables in db/db mice, but GSIS, insulin and triacylglycerol content were not affected. In db/db mice, liraglutide increased gene expression associated with cell differentiation, proliferation and anti-apoptosis, and suppressed gene expression involved in pro-apoptosis; it had no effect on genes related to oxidative stress or ER stress. Morphometric results for cell proliferation, cell apoptosis and oxidative stress in db/db mice islets were consistent with the results of the gene expression analysis. Liraglutide increases beta cell mass not only by directly regulating cell kinetics, but also by suppressing oxidative and ER stress, secondary to amelioration of glucolipotoxicity.
登录
查看更多内容
影响因子：
4.8
作者：
FRODIN, M;SEKINE, N;VANOBBERGHEN, E
通讯作者：
VANOBBERGHEN, E
影响因子：
4.8
作者：
Hui, HX;Nourparvar, A;Perfetti, R
通讯作者：
Perfetti, R
影响因子：
8.2
作者：
Buteau, J;Roduit, R;Prentki, M
通讯作者：
Prentki, M
影响因子：
4
作者：
Friedrichsen, BN;Neubauer, N;Moldrup, A
通讯作者：
Moldrup, A
影响因子：
29.4
作者：
Jensen, JN;Cameron, E;Jensen, J
通讯作者：
Jensen, J