Imeglimin exerts favorable effects on pancreatic β-cells by improving morphology in mitochondria and increasing the number of insulin granules.
Imeglimin exerts favorable effects on pancreatic β-cells by improving morphology in mitochondria and increasing the number of insulin granules.
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Imeglimin通过改善线粒体的形态和增加胰岛素颗粒的数量对胰腺β细胞发挥有利的作用。
DOI：
10.1038/s41598-022-17657-3
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发表时间：
2022-08-02
影响因子：
4.6
通讯作者：
Kaneto, Hideaki
中科院分区：
文献类型：
--
作者：
Sanada, Junpei;Obata, Atsushi;Fushimi, Yoshiro;Kimura, Tomohiko;Shimoda, Masashi;Ikeda, Tomoko;Nogami, Yuka;Obata, Yoshiyuki;Yamasaki, Yuki;Nakanishi, Shuhei;Mune, Tomoatsu;Kaku, Kohei;Kaneto, Hideaki
Imeglimin是一种在日本上市的抗糖尿病新药(Twymeig®)，在糖尿病研究领域和临床实践中一直受到关注。在这项研究中，我们评估了伊美利明对胰腺β细胞的影响。首先，单剂量服用伊美利明可增加β细胞的胰岛素分泌，并降低2型糖尿病db/db小鼠的血糖水平。此外，单剂量注射伊美利明显著增加非糖尿病db/m小鼠胰岛对葡萄糖的反应而分泌的胰岛素。第二，在口服葡萄糖耐量试验中，使用伊美利明进行为期4周的慢性治疗，可促进糖尿病db/db小鼠的胰岛素分泌，改善血糖控制。此外，电子显微镜图像显示，伊美利明对2型糖尿病db/db和KK-Ay小鼠β细胞线粒体的形态有良好的影响，并显著增加了胰岛素颗粒的数量。最后，伊美利明降低了β细胞凋亡性死亡的百分率，同时降低了β细胞中与凋亡和炎症相关的各种基因的表达水平。综上所述，伊美利明可直接促进β细胞对葡萄糖的胰岛素分泌，增加胰岛素颗粒数量，改善β细胞线粒体的形态，减少2型糖尿病小鼠β细胞的凋亡性死亡，最终改善血糖控制。
Imeglimin is a new anti-diabetic drug commercialized in Japan (Twymeeg®) and has been drawing much attention in diabetes research area as well as in clinical practice. In this study, we evaluated the effect of imeglimin on pancreatic β-cells. First, single-dose administration of imeglimin enhanced insulin secretion from β-cells and decreased blood glucose levels in type 2 diabetic db/db mice. In addition, single-dose administration of imeglimin significantly augmented insulin secretion in response to glucose from islets isolated from non-diabetic db/m mice. Second, during an oral glucose tolerance test 4-week chronic treatment with imeglimin enhanced insulin secretion and ameliorated glycemic control in diabetic db/db mice. Furthermore, the examination with electron microscope image showed that imeglimin exerted favorable effects on morphology in β-cell mitochondria and substantially increased the number of insulin granules in type 2 diabetic db/db and KK-Ay mice. Finally, imeglimin reduced the percentage of apoptotic β-cell death which was accompanied by reduced expression levels of various genes related to apoptosis and inflammation in β-cells. Taken together, imeglimin directly enhances insulin secretion in response to glucose from β-cells, increases the number of insulin granules, exerts favorable effects on morphology in β-cell mitochondria, and reduces apoptotic β-cell death in type 2 diabetic mice, which finally leads to amelioration of glycemic control.
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影响因子：
--
作者：
Hallakou-Bozec S;Kergoat M;Moller DE;Bolze S
通讯作者：
Bolze S
影响因子：
4.6
作者：
Fushimi Y;Obata A;Sanada J;Nogami Y;Ikeda T;Yamasaki Y;Obata Y;Shimoda M;Nakanishi S;Mune T;Kaku K;Kaneto H
通讯作者：
Kaneto H
影响因子：
7.7
作者：
Vial, Guillaume;Chauvin, Marie-Agnes;Rieusset, Jennifer
通讯作者：
Rieusset, Jennifer
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
8.2
作者：
Iwashita, N.;Uchida, T.;Watada, H.
通讯作者：
Watada, H.