Antiaging Gene Klotho Attenuates Pancreatic β-Cell Apoptosis in Type 1 Diabetes

摘要: Apoptosis is the major cause of death insulin-producing β-cells in type 1 diabetes mellitus (T1DM). Klotho a recently discovered antiaging gene. We found that gene expressed pancreatic β-cells. Interestingly, halplodeficiency (KL(+/-)) exacerbated streptozotocin (STZ)-induced (a model T1DM), including hyperglycemia, glucose intolerance, diminished islet insulin storage, and increased apoptotic Conversely, vivo β-cell-specific expression mouse (mKL) attenuated β-cell apoptosis prevented STZ-induced diabetes. mKL promoted cell adhesion to collagen IV, FAK Akt phosphorylation, inhibited caspase 3 cleavage cultured MIN6 abolished STZ- TNFα-induced inhibition cleavage, apoptosis. These promoting effects can be by blocking integrin β1. Therefore, these cell-based studies indicated protected inhibiting through activation β1-FAK/Akt pathway, leading cleavage. In an autoimmune T1DM (NOD), we showed improved tolerance, apoptosis, enhanced storage β-cells, plasma levels. The beneficial effect delivery likely due attenuation T-cell infiltration islets NOD mice. Overall, our results demonstrate for first time via attenuating