| First Author | Nishiyama K | Year | 2023 |
| Journal | Endocrinology | Volume | 164 |
| Issue | 8 | PubMed ID | 37314160 |
| Mgi Jnum | J:339317 | Mgi Id | MGI:7516438 |
| Doi | 10.1210/endocr/bqad095 | Citation | Nishiyama K, et al. (2023) Protective Effects of Imeglimin and Metformin Combination Therapy on beta-Cells in db/db Male Mice. Endocrinology 164(8) |
| abstractText | Imeglimin and metformin act in metabolic organs, including beta-cells, via different mechanisms. In the present study, we investigated the impacts of imeglimin, metformin, or their combination (Imeg + Met) on beta-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 beta-cell mass by enhancing beta-cell proliferation and ameliorating beta-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 beta-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 beta-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 beta-cell mass in db/db mice, probably through direct action on beta-cells, suggesting a potential strategy for protecting beta-cells in the treatment of type 2 diabetes. |
