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Overview
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Background
MSDC-0160 is a prototype mTOT-modulating insulin sensitizer [1].MSDC-0160 is a thiazolidinedione insulin sensitizer without the peroxisome proliferator–activated receptor-γ (PPAR-γ)-dependent side effects. Co-incubation of islets with MSDC-0160 and IGF-1 reduces the resistance of insulin-signaling pathway and preserves insulin content. MSDC-0160 at 50μM alone also prevents the loss of insulin content significantly. Besides that, treatment of MSDC-0160 increases the phosphorylation of AMPK and reduces mTOR phosphorylation. Moreover, MSDC-0160 is also found to display pro-survival effects in human islets via reducing the level of cleaved caspase-3 and increasing the expression of apoptosis-related genes such as bcl2. In addition, MSDC-0160 exerts prevention of nuclear translocation with β-catenin localized on the cell membrane or cytoplasm in human β-cells [1].
[1] Rohatgi N, Aly H, Marshall C A, et al. Novel insulin sensitizer modulates nutrient sensing pathways and maintains β-cell phenotype in human islets. PloS one, 2013, 8(5): e62012.
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