Matches in SemOpenAlex for { <https://semopenalex.org/work/W2896592854> ?p ?o ?g. }
- W2896592854 abstract "Abstract β-cell proliferation induction is a promising therapeutic strategy to restore β-cell mass. By screening small molecules in a transgenic zebrafish model of type 1 diabetes, we identified inhibitors of non-canonical IκB kinases (IKKs), TANK-binding kinase 1 (TBK1) and IκB kinase ε (IKKε), as enhancers of β-cell regeneration. The most potent β-cell regeneration enhancer was a cinnamic acid derivative (E)-3-(3- p henylbenzo[c] i soxazol-5-yl) a crylic a cid (PIAA), which, acting through the cAMP-dependent protein kinase A (PKA), stimulated β-cell-specific proliferation by increasing cyclic AMP (cAMP) levels and mechanistic target of rapamycin (mTOR) activity. A combination of PIAA and cilostamide, an inhibitor of β-cell-enriched cAMP hydrolyzing enzyme phosphodiesterase (PDE) 3, enhanced β-cell proliferation, whereas overexpression of PDE3 blunted the mitogenic effect of PIAA in zebrafish. PIAA augmented proliferation of INS-1β-cells and β-cells in mammalian islets including human islets with elevation in cAMP levels and insulin secretion. PIAA improved glycemic control in streptozotocin (STZ)-induced diabetic mice with increases in β-cell proliferation, β-cell area, and insulin content in the pancreas. Collectively, these data reveal an evolutionarily conserved and critical role of TBK1/IKKε suppression in expanding functional β-cell mass." @default.
- W2896592854 created "2018-10-26" @default.
- W2896592854 creator A5011208920 @default.
- W2896592854 creator A5021883063 @default.
- W2896592854 creator A5025609028 @default.
- W2896592854 creator A5032119688 @default.
- W2896592854 creator A5038333333 @default.
- W2896592854 creator A5048523287 @default.
- W2896592854 creator A5063310122 @default.
- W2896592854 creator A5066507908 @default.
- W2896592854 creator A5070228740 @default.
- W2896592854 creator A5083436505 @default.
- W2896592854 creator A5088157671 @default.
- W2896592854 creator A5091420930 @default.
- W2896592854 date "2018-10-22" @default.
- W2896592854 modified "2023-09-26" @default.
- W2896592854 title "Inhibition of TBK1/IKKε Promotes Regeneration of Pancreatic β-cells" @default.
- W2896592854 cites W1502350494 @default.
- W2896592854 cites W1574602595 @default.
- W2896592854 cites W1966270876 @default.
- W2896592854 cites W1968995247 @default.
- W2896592854 cites W1979535675 @default.
- W2896592854 cites W1982782912 @default.
- W2896592854 cites W1983109395 @default.
- W2896592854 cites W1983596329 @default.
- W2896592854 cites W1989573190 @default.
- W2896592854 cites W1996839988 @default.
- W2896592854 cites W2003454094 @default.
- W2896592854 cites W2011282245 @default.
- W2896592854 cites W2016147073 @default.
- W2896592854 cites W2022101780 @default.
- W2896592854 cites W2025202152 @default.
- W2896592854 cites W2028200523 @default.
- W2896592854 cites W2032156343 @default.
- W2896592854 cites W2033863085 @default.
- W2896592854 cites W2037754889 @default.
- W2896592854 cites W2039096764 @default.
- W2896592854 cites W2039235909 @default.
- W2896592854 cites W2041739600 @default.
- W2896592854 cites W2041926656 @default.
- W2896592854 cites W2043431165 @default.
- W2896592854 cites W2047745287 @default.
- W2896592854 cites W2051338604 @default.
- W2896592854 cites W2060267055 @default.
- W2896592854 cites W2060591168 @default.
- W2896592854 cites W2062756785 @default.
- W2896592854 cites W2063720970 @default.
- W2896592854 cites W2066243203 @default.
- W2896592854 cites W2066659565 @default.
- W2896592854 cites W2075712485 @default.
- W2896592854 cites W2079075339 @default.
- W2896592854 cites W2079332279 @default.
- W2896592854 cites W2084224574 @default.
- W2896592854 cites W2089109393 @default.
- W2896592854 cites W2091800772 @default.
- W2896592854 cites W2094941511 @default.
- W2896592854 cites W2104479866 @default.
- W2896592854 cites W2106293966 @default.
- W2896592854 cites W2110528304 @default.
- W2896592854 cites W2111352469 @default.
- W2896592854 cites W2113532020 @default.
- W2896592854 cites W2117290383 @default.
- W2896592854 cites W2120687067 @default.
- W2896592854 cites W2131933743 @default.
- W2896592854 cites W2132358997 @default.
- W2896592854 cites W2145824107 @default.
- W2896592854 cites W2147592527 @default.
- W2896592854 cites W2148147368 @default.
- W2896592854 cites W2153134360 @default.
- W2896592854 cites W2156710421 @default.
- W2896592854 cites W2158438063 @default.
- W2896592854 cites W2162033174 @default.
- W2896592854 cites W2166291320 @default.
- W2896592854 cites W2168531121 @default.
- W2896592854 cites W2169337437 @default.
- W2896592854 cites W2169537091 @default.
- W2896592854 cites W2171968212 @default.
- W2896592854 cites W2181908737 @default.
- W2896592854 cites W2221658929 @default.
- W2896592854 cites W2258420810 @default.
- W2896592854 cites W2277920967 @default.
- W2896592854 cites W2322477027 @default.
- W2896592854 cites W2323566388 @default.
- W2896592854 cites W2328791756 @default.
- W2896592854 cites W2333335236 @default.
- W2896592854 cites W2518918481 @default.
- W2896592854 cites W2593816418 @default.
- W2896592854 cites W2786396437 @default.
- W2896592854 cites W2790048311 @default.
- W2896592854 doi "https://doi.org/10.1038/s41598-018-33875-0" @default.
- W2896592854 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6197228" @default.
- W2896592854 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30349097" @default.
- W2896592854 hasPublicationYear "2018" @default.
- W2896592854 type Work @default.
- W2896592854 sameAs 2896592854 @default.
- W2896592854 citedByCount "23" @default.
- W2896592854 countsByYear W28965928542019 @default.
- W2896592854 countsByYear W28965928542020 @default.
- W2896592854 countsByYear W28965928542021 @default.
- W2896592854 countsByYear W28965928542022 @default.