| First Author | Lin Y | Year | 2015 |
| Journal | Diabetes | Volume | 64 |
| Issue | 4 | Pages | 1444-58 |
| PubMed ID | 25377875 | Mgi Jnum | J:246322 |
| Mgi Id | MGI:5923482 | Doi | 10.2337/db14-0632 |
| Citation | Lin Y, et al. (2015) In vivo pancreatic beta-cell-specific expression of antiaging gene Klotho: a novel approach for preserving beta-cells in type 2 diabetes. Diabetes 64(4):1444-58 |
| abstractText | Protein expression of an antiaging gene, Klotho, was depleted in pancreatic islets in patients with type 2 diabetes mellitus (T2DM) and in db/db mice, an animal model of T2DM. The objective of this study was to investigate whether in vivo expression of Klotho would preserve pancreatic beta-cell function in db/db mice. We report for the first time that beta-cell-specific expression of Klotho attenuated the development of diabetes in db/db mice. beta-Cell-specific expression of Klotho decreased hyperglycemia and enhanced glucose tolerance. The beneficial effects of Klotho were associated with significant improvements in T2DM-induced decreases in number of beta-cells, insulin storage levels in pancreatic islets, and glucose-stimulated insulin secretion from pancreatic islets, which led to increased blood insulin levels in diabetic mice. In addition, beta-cell-specific expression of Klotho decreased intracellular superoxide levels, oxidative damage, apoptosis, and DNAJC3 (a marker for endoplasmic reticulum stress) in pancreatic islets. Furthermore, beta-cell-specific expression of Klotho increased expression levels of Pdx-1 (insulin transcription factor), PCNA (a marker of cell proliferation), and LC3 (a marker of autophagy) in pancreatic islets in db/db mice. These results reveal that beta-cell-specific expression of Klotho improves beta-cell function and attenuates the development of T2DM. Therefore, in vivo expression of Klotho may offer a novel strategy for protecting beta-cells in T2DM. |
