Determination of the Effects and Mechanisms of Action of Compounds Related to Various Molecular Pathways on the Regeneration of β-Cells In-Vivo
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Chemicals associated with anti-inflammatory biological signaling pathways are known to be effective methods of alleviating the symptoms for numerous diseases and medical conditions, including diabetes. Recently, an increasing number of studies are analyzing biological signaling compounds in the context of having the potential to directly stimulate regeneration of pancreatic β-cells. Few efforts have been successful in demonstrating and characterizing the relationship between compounds associated with anti-inflammatory pathways and the proliferation and regeneration capability of β-cells. This study aimed to test the effects of chemicals with anti-inflammatory effects on the up-regulation of insulin regeneration in zebrafish embryos. The ultimate goal was to discover specific anti-inflammatory drugs that have the potential to treat diabetes by directly increasing the size and insulin-secreting functionality of the β-cell mass, as well as to determine their mechanisms of action. It was discovered that the small molecule BX-795, which acts as an anti-inflammatory agent and inhibits the catalytic activity of the protein kinases tank-binding kinase 1 (TBK1) and Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKKε) of the toll-like receptor biological signaling pathway, has great potential as a successful inducer of β-cell regeneration following ablation of β-cells. This compound and the toll-like receptor pathway have potential to be involved in the reversal of Type I diabetes.