Matches in SemOpenAlex for { <https://semopenalex.org/work/W2603721103> ?p ?o ?g. }
- W2603721103 endingPage "632" @default.
- W2603721103 startingPage "624" @default.
- W2603721103 abstract "The generation of low-molecular-weight protein tyrosine phosphatase (LMPTP) knockout mice combined with the identification of a small-molecule uncompetitive LMPTP inhibitor reveals a role for LMPTP in regulating insulin resistance. Obesity-associated insulin resistance plays a central role in type 2 diabetes. As such, tyrosine phosphatases that dephosphorylate the insulin receptor (IR) are potential therapeutic targets. The low-molecular-weight protein tyrosine phosphatase (LMPTP) is a proposed IR phosphatase, yet its role in insulin signaling in vivo has not been defined. Here we show that global and liver-specific LMPTP deletion protects mice from high-fat diet-induced diabetes without affecting body weight. To examine the role of the catalytic activity of LMPTP, we developed a small-molecule inhibitor with a novel uncompetitive mechanism, a unique binding site at the opening of the catalytic pocket, and an exquisite selectivity over other phosphatases. This inhibitor is orally bioavailable, and it increases liver IR phosphorylation in vivo and reverses high-fat diet-induced diabetes. Our findings suggest that LMPTP is a key promoter of insulin resistance and that LMPTP inhibitors would be beneficial for treating type 2 diabetes." @default.
- W2603721103 created "2017-04-07" @default.
- W2603721103 creator A5000061417 @default.
- W2603721103 creator A5003372721 @default.
- W2603721103 creator A5007919640 @default.
- W2603721103 creator A5011707402 @default.
- W2603721103 creator A5020556900 @default.
- W2603721103 creator A5021593173 @default.
- W2603721103 creator A5021908393 @default.
- W2603721103 creator A5023525157 @default.
- W2603721103 creator A5024369051 @default.
- W2603721103 creator A5024374384 @default.
- W2603721103 creator A5026853575 @default.
- W2603721103 creator A5050077508 @default.
- W2603721103 creator A5050138752 @default.
- W2603721103 creator A5050815439 @default.
- W2603721103 creator A5053774360 @default.
- W2603721103 creator A5054442364 @default.
- W2603721103 creator A5059779329 @default.
- W2603721103 creator A5070154302 @default.
- W2603721103 creator A5072059626 @default.
- W2603721103 creator A5076365556 @default.
- W2603721103 creator A5077618800 @default.
- W2603721103 creator A5078247081 @default.
- W2603721103 creator A5090001946 @default.
- W2603721103 date "2017-03-27" @default.
- W2603721103 modified "2023-10-01" @default.
- W2603721103 title "Diabetes reversal by inhibition of the low-molecular-weight tyrosine phosphatase" @default.
- W2603721103 cites W1624505911 @default.
- W2603721103 cites W164817101 @default.
- W2603721103 cites W1789274326 @default.
- W2603721103 cites W1978137896 @default.
- W2603721103 cites W1979069875 @default.
- W2603721103 cites W1985076356 @default.
- W2603721103 cites W1987847325 @default.
- W2603721103 cites W1999863139 @default.
- W2603721103 cites W2001641653 @default.
- W2603721103 cites W2007912187 @default.
- W2603721103 cites W2013122081 @default.
- W2603721103 cites W2014887370 @default.
- W2603721103 cites W2016718617 @default.
- W2603721103 cites W2021500473 @default.
- W2603721103 cites W2022786966 @default.
- W2603721103 cites W2024235773 @default.
- W2603721103 cites W2024849265 @default.
- W2603721103 cites W2024849484 @default.
- W2603721103 cites W2038840577 @default.
- W2603721103 cites W2038961236 @default.
- W2603721103 cites W2039718498 @default.
- W2603721103 cites W2043509228 @default.
- W2603721103 cites W2043617798 @default.
- W2603721103 cites W2052389378 @default.
- W2603721103 cites W2058205536 @default.
- W2603721103 cites W2062055994 @default.
- W2603721103 cites W2072962748 @default.
- W2603721103 cites W2077382512 @default.
- W2603721103 cites W2080418501 @default.
- W2603721103 cites W2083042788 @default.
- W2603721103 cites W2083193528 @default.
- W2603721103 cites W2086120012 @default.
- W2603721103 cites W2104656412 @default.
- W2603721103 cites W2121668468 @default.
- W2603721103 cites W2123229219 @default.
- W2603721103 cites W2127143218 @default.
- W2603721103 cites W2144081223 @default.
- W2603721103 cites W2145490597 @default.
- W2603721103 cites W2147067786 @default.
- W2603721103 cites W2148457238 @default.
- W2603721103 cites W2151214732 @default.
- W2603721103 cites W2156763911 @default.
- W2603721103 cites W2163341755 @default.
- W2603721103 cites W2163913710 @default.
- W2603721103 cites W2164438527 @default.
- W2603721103 cites W2165813993 @default.
- W2603721103 cites W2166507757 @default.
- W2603721103 cites W2171290692 @default.
- W2603721103 cites W2180229411 @default.
- W2603721103 cites W2334411593 @default.
- W2603721103 cites W2410143838 @default.
- W2603721103 cites W320360378 @default.
- W2603721103 cites W4248872320 @default.
- W2603721103 doi "https://doi.org/10.1038/nchembio.2344" @default.
- W2603721103 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5435566" @default.
- W2603721103 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28346406" @default.
- W2603721103 hasPublicationYear "2017" @default.
- W2603721103 type Work @default.
- W2603721103 sameAs 2603721103 @default.
- W2603721103 citedByCount "52" @default.
- W2603721103 countsByYear W26037211032017 @default.
- W2603721103 countsByYear W26037211032018 @default.
- W2603721103 countsByYear W26037211032019 @default.
- W2603721103 countsByYear W26037211032020 @default.
- W2603721103 countsByYear W26037211032021 @default.
- W2603721103 countsByYear W26037211032022 @default.
- W2603721103 countsByYear W26037211032023 @default.
- W2603721103 crossrefType "journal-article" @default.
- W2603721103 hasAuthorship W2603721103A5000061417 @default.
- W2603721103 hasAuthorship W2603721103A5003372721 @default.