- 【Updated on May 12, 2025】 Integration of CiNii Dissertations and CiNii Books into CiNii Research
- Trial version of CiNii Research Automatic Translation feature is available on CiNii Labs
- Suspension and deletion of data provided by Nikkei BP
- Regarding the recording of “Research Data” and “Evidence Data”
Protective Effects of Imeglimin and Metformin Combination Therapy on β-Cells in db/db Male Mice
-
- Kuniyuki Nishiyama
- Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University , Maebashi 371-8512 , Japan
-
- Masato Ono
- Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University , Yokohama 236-0004 , Japan
-
- Takahiro Tsuno
- Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University , Maebashi 371-8512 , Japan
-
- Ryota Inoue
- Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University , Maebashi 371-8512 , Japan
-
- Ayako Fukunaka
- Laboratory of Developmental Biology and Metabolism, Institute for Molecular and Cellular Regulation (IMCR), Gunma University , Maebashi 371-8512 , Japan
-
- Tomoko Okuyama
- Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University , Yokohama 236-0004 , Japan
-
- Mayu Kyohara
- Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University , Yokohama 236-0004 , Japan
-
- Yu Togashi
- Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University , Yokohama 236-0004 , Japan
-
- Setsuko Fukushima
- Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University , Maebashi 371-8512 , Japan
-
- Takuto Atsumi
- Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University , Maebashi 371-8512 , Japan
-
- Aoi Sato
- Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University , Maebashi 371-8512 , Japan
-
- Asuka Tsurumoto
- Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University , Maebashi 371-8512 , Japan
-
- Chisato Sakai
- Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University , Maebashi 371-8512 , Japan
-
- Yoshio Fujitani
- Laboratory of Developmental Biology and Metabolism, Institute for Molecular and Cellular Regulation (IMCR), Gunma University , Maebashi 371-8512 , Japan
-
- Yasuo Terauchi
- Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University , Yokohama 236-0004 , Japan
-
- Shuichi Ito
- Department of Pediatrics, Graduate School of Medicine, Yokohama City University , Yokohama 236-0004 , Japan
-
- Jun Shirakawa
- Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University , Maebashi 371-8512 , Japan
Description
<jats:title>Abstract</jats:title> <jats:p>Imeglimin and metformin act in metabolic organs, including β-cells, via different mechanisms. In the present study, we investigated the impacts of imeglimin, metformin, or their combination (Imeg + Met) on β-cells, the liver, and adipose tissues in db/db mice. Imeglimin, metformin, or Imeg + Met treatment had no significant effects on glucose tolerance, insulin sensitivity, respiratory exchange ratio, or locomotor activity in db/db mice. The responsiveness of insulin secretion to glucose was recovered by Imeg + Met treatment. Furthermore, Imeg + Met treatment increased β-cell mass by enhancing β-cell proliferation and ameliorating β-cell apoptosis in db/db mice. Hepatic steatosis, the morphology of adipocytes, adiposity assessed by computed tomography, and the expression of genes related to glucose or lipid metabolism and inflammation in the liver and fat tissues showed no notable differences in db/db mice. Global gene expression analysis of isolated islets indicated that the genes related to regulation of cell population proliferation and negative regulation of cell death were enriched by Imeg + Met treatment in db/db islets. In vitro culture experiments confirmed the protective effects of Imeg + Met against β-cell apoptosis. The expression of Snai1, Tnfrsf18, Pdcd1, Mmp9, Ccr7, Egr3, and Cxcl12, some of which have been linked to apoptosis, in db/db islets was attenuated by Imeg + Met. Treatment of a β-cell line with Imeg + Met prevented apoptosis induced by hydrogen peroxide or palmitate. Thus, the combination of imeglimin and metformin is beneficial for the maintenance of β-cell mass in db/db mice, probably through direct action on β-cells, suggesting a potential strategy for protecting β-cells in the treatment of type 2 diabetes.</jats:p>
Journal
-
- Endocrinology
-
Endocrinology 164 (8), 2023-06-14
The Endocrine Society
