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• W2338857512 endingPage "1208" @default.
• W2338857512 startingPage "1198" @default.
• W2338857512 abstract "Previous studies utilizing PUGNAc, the most widely used β-N-acetylglucosaminidase (OGA) inhibitor to increase global O-N-acetylglucosamine (GlcNAc) levels, have reported a variety of effects including insulin resistance as a direct result of elevated O-GlcNAc levels. The notion of OGA inhibition causing insulin resistance was not replicated in studies in which elevated global O-GlcNAc levels were achieved using two other OGA inhibitors. Related to insulin action, work by others has suggested that O-GlcNAc elevation may inhibit the anti-apoptotic action of insulin. Thus, we examined the pro-survival action of insulin upon serum deprivation in the presence of PUGNAc as well as two selective OGA inhibitors (GlcNAcstatin-g and Thiamet-G), and a selective lysosomal hexosaminidase inhibitor (INJ2). We established that PUGNAc inhibits the pro-survival action of insulin but this effect is not recapitulated by the selective OGA inhibitors suggesting that elevation in O-GlcNAc levels alone is not responsible for PUGNAc's effect on the anti-apoptotic action of insulin. Further, we demonstrate that a selective hexosaminidase A/B (HexA/B) inhibitor does not impact insulin action suggesting that PUGNAc's effect is not due to inhibition of lysosomal hexosaminidase. Finally, we tested a combination of selective OGA and lysosomal hexosaminidase inhibitors but were not able to recapitulate the inhibition of insulin action generated by PUGNAc alone. These results strongly suggest that the defect in insulin action upon PUGNAc treatment does not derive from its inhibition of OGA or HexA/B, and that there is an unknown target of PUGNAc that is the likely culprit in inhibiting the protective effect of insulin from apoptosis." @default.
• W2338857512 created "2016-06-24" @default.
• W2338857512 creator A5002084451 @default.
• W2338857512 creator A5047989158 @default.
• W2338857512 creator A5067500932 @default.
• W2338857512 date "2016-11-14" @default.
• W2338857512 modified "2023-09-26" @default.
• W2338857512 title "Dissecting PUGNAc-mediated inhibition of the pro-survival action of insulin" @default.
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• W2338857512 doi "https://doi.org/10.1093/glycob/cww043" @default.
• W2338857512 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5884396" @default.
• W2338857512 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27072814" @default.
• W2338857512 hasPublicationYear "2016" @default.
• W2338857512 type Work @default.
• W2338857512 sameAs 2338857512 @default.

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