| First Author | Asrih M | Year | 2022 |
| Journal | Mol Cell Endocrinol | Volume | 541 |
| Pages | 111503 | PubMed ID | 34763008 |
| Mgi Jnum | J:319793 | Mgi Id | MGI:6865546 |
| Doi | 10.1016/j.mce.2021.111503 | Citation | Asrih M, et al. (2022) Growth differentiation factor-15 prevents glucotoxicity and connexin-36 downregulation in pancreatic beta-cells. Mol Cell Endocrinol 541:111503 |
| abstractText | Pancreatic beta cell dysfunction is a hallmark of type 2 diabetes. Growth differentiation factor 15 (GDF15), which is an energy homeostasis regulator, has been shown to improve several metabolic parameters in the context of diabetes. However, its effects on pancreatic beta-cell remain to be identified. We, therefore, performed experiments using cell models and histological sectioning of wild-type and knock-out GDF15 mice to determine the effect of GDF15 on insulin secretion and cell viability. A bioinformatics analysis was performed to identify GDF15-correlated genes. GDF15 prevents glucotoxicity-mediated altered glucose-stimulated insulin secretion (GSIS) and connexin-36 downregulation. Inhibition of endogenous GDF15 reduced GSIS in cultured mouse beta-cells under standard conditions while it had no impact on GSIS in cells exposed to glucolipotoxicity, which is a diabetogenic condition. Furthermore, this inhibition exacerbated glucolipotoxicity-reduced cell survival. This suggests that endogenous GDF15 in beta-cell is required for cell survival but not GSIS in the context of glucolipotoxicity. |
