A novel SIRT1 activator E6155 improves insulin sensitivity in type 2 diabetic KKA_y mice.

ABSTRACT: Sirtuin 1 (SIRT1) is an NAD⁺-dependent protein deacetylase that plays a critical role in controlling energy metabolism, stress response and aging. Hence, enhancing SIRT1 activity could be a potential therapeutic strategy to treat metabolic diseases such as diabetes. However, pharmacological activators for SIRT1 are scarce to date. In this study, using the optimized high throughput screening, we identified E6155, a piperazine 1, 4- diamide compound, as a new small molecular activator of SIRT1. We further found that E6155 significantly upregulated glucose uptake in cultured normal liver cells and skeletal muscle cells through increasing SIRT1 deacetylase activity. In type 2 diabetic KKA_y mice, E6155 treatment markedly decreased the level of fasting glucose. Moreover, E6

SUBMITTER: Liu P 

PROVIDER: S-EPMC5898622 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature