کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8293576 1536745 2018 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A novel SIRT1 activator E6155 improves insulin sensitivity in type 2 diabetic KKAy mice
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
A novel SIRT1 activator E6155 improves insulin sensitivity in type 2 diabetic KKAy mice
چکیده انگلیسی
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 KKAy mice, E6155 treatment markedly decreased the level of fasting glucose. Moreover, E6155 improved oral glucose tolerance and insulin tolerance. Euglycemic clamp and the homeostasis model assessment of insulin resistance index showed that E6155 ameliorated the insulin resistance and increased insulin sensitivity in diabetic mice. Mechanistically, we observed that the antidiabetic effects of E6155 were involved in SIRT1 dependent activation of LKB1/AMPK and IRS1/AKT pathways. In conclusion, our findings identified E6155 as a novel SIRT1 activator and suggested that E6155 could be a promising drug candidate for treating insulin resistance and diabetes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 498, Issue 3, 6 April 2018, Pages 633-639
نویسندگان
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