Imeglimin exerts favorable effects on pancreatic β-cells by improving morphology in mitochondria and increasing the number of insulin granules
Abstract 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 e...
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| Format: | Article |
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Nature Portfolio
2022-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-17657-3 |
| _version_ | 1811315313384357888 |
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| author | Junpei Sanada Atsushi Obata Yoshiro Fushimi Tomohiko Kimura Masashi Shimoda Tomoko Ikeda Yuka Nogami Yoshiyuki Obata Yuki Yamasaki Shuhei Nakanishi Tomoatsu Mune Kohei Kaku Hideaki Kaneto |
| author_facet | Junpei Sanada Atsushi Obata Yoshiro Fushimi Tomohiko Kimura Masashi Shimoda Tomoko Ikeda Yuka Nogami Yoshiyuki Obata Yuki Yamasaki Shuhei Nakanishi Tomoatsu Mune Kohei Kaku Hideaki Kaneto |
| author_sort | Junpei Sanada |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-13T11:28:02Z |
| format | Article |
| id | doaj.art-da7310c49b754fb8a6467d24aca5b8f8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T11:28:02Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-da7310c49b754fb8a6467d24aca5b8f82022-12-22T02:48:39ZengNature PortfolioScientific Reports2045-23222022-08-0112111110.1038/s41598-022-17657-3Imeglimin exerts favorable effects on pancreatic β-cells by improving morphology in mitochondria and increasing the number of insulin granulesJunpei Sanada0Atsushi Obata1Yoshiro Fushimi2Tomohiko Kimura3Masashi Shimoda4Tomoko Ikeda5Yuka Nogami6Yoshiyuki Obata7Yuki Yamasaki8Shuhei Nakanishi9Tomoatsu Mune10Kohei Kaku11Hideaki Kaneto12Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical SchoolDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical SchoolDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical SchoolDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical SchoolDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical SchoolDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical SchoolDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical SchoolDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical SchoolDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical SchoolDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical SchoolDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical SchoolDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical SchoolDepartment of Diabetes, Endocrinology and Metabolism, Kawasaki Medical SchoolAbstract 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.https://doi.org/10.1038/s41598-022-17657-3 |
| spellingShingle | Junpei Sanada Atsushi Obata Yoshiro Fushimi Tomohiko Kimura Masashi Shimoda Tomoko Ikeda Yuka Nogami Yoshiyuki Obata Yuki Yamasaki Shuhei Nakanishi Tomoatsu Mune Kohei Kaku Hideaki Kaneto Imeglimin exerts favorable effects on pancreatic β-cells by improving morphology in mitochondria and increasing the number of insulin granules Scientific Reports |
| title | Imeglimin exerts favorable effects on pancreatic β-cells by improving morphology in mitochondria and increasing the number of insulin granules |
| title_full | Imeglimin exerts favorable effects on pancreatic β-cells by improving morphology in mitochondria and increasing the number of insulin granules |
| title_fullStr | Imeglimin exerts favorable effects on pancreatic β-cells by improving morphology in mitochondria and increasing the number of insulin granules |
| title_full_unstemmed | Imeglimin exerts favorable effects on pancreatic β-cells by improving morphology in mitochondria and increasing the number of insulin granules |
| title_short | Imeglimin exerts favorable effects on pancreatic β-cells by improving morphology in mitochondria and increasing the number of insulin granules |
| title_sort | imeglimin exerts favorable effects on pancreatic β cells by improving morphology in mitochondria and increasing the number of insulin granules |
| url | https://doi.org/10.1038/s41598-022-17657-3 |
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