Search: id:"swepub:oai:DiVA.org:his-13784" >
Suppression of 5 '-...
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Kulkarni, Sameer S.Karolinska Institutet, Stockholm, Sweden
(author)
Suppression of 5 '-Nucleotidase Enzymes Promotes AMP-activated Protein Kinase (AMPK) Phosphorylation and Metabolism in Human and Mouse Skeletal Muscle
- Article/chapterEnglish2011
Publisher, publication year, extent ...
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American Society for Biochemistry and Molecular Biology, Inc.2011
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Numbers
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LIBRIS-ID:oai:DiVA.org:his-13784
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https://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-13784URI
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https://doi.org/10.1074/jbc.M111.268292DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:123452000URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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The 5'-nucleotidase (NT5) family of enzyme dephosphorylates non-cyclic nucleoside monophosphates to produce nucleosides and inorganic phosphates. We hypothesized that gene silencing of NT5 enzymes to increase the intracellular availability of AMP would increase AMP-activated protein kinase (AMPK) activity and metabolism. We determined the role of cytosolic NT5 in metabolic responses linked to the development of insulin resistance in obesity and type 2 diabetes. Using siRNA to silence NT5C2 expression in cultured human myotubes, we observed a 2-fold increase in the AMP/ATP ratio, a 2.4-fold increase in AMPK phosphorylation (Thr(172)), and a 2.8-fold increase in acetyl-CoA carboxylase phosphorylation (Ser(79)) (p<0.05). siRNA silencing of NT5C2 expression increased palmitate oxidation by 2-fold in the absence and by 8-fold in the presence of 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside. This was paralleled by an increase in glucose transport and a decrease in glucose oxidation, incorporation into glycogen, and lactate release from NT5C2-depleted myotubes. Gene silencing of NT5C1A by shRNA injection and electroporation in mouse tibialis anterior muscle reduced protein content (60%; p<0.05) and increased phosphorylation of AMPK (60%; p<0.05) and acetyl-CoA carboxylase (50%; p<0.05) and glucose uptake (20%; p<0.05). Endogenous expression of NT5C enzymes inhibited basal lipid oxidation and glucose transport in skeletal muscle. Reduction of 5'-nucleotidase expression or activity may promote metabolic flexibility in type 2 diabetes.
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Added entries (persons, corporate bodies, meetings, titles ...)
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Karlsson, Håkan K. R.Karolinska Institutet,Karolinska Institutet, Stockholm, Sweden
(author)
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Szekeres, FerencKarolinska Institutet,Karolinska Institutet, Stockholm, Sweden(Swepub:his)szef
(author)
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Chibalin, Alexander V.Karolinska Institutet,Karolinska Institutet, Stockholm, Sweden
(author)
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Krook, AnnaKarolinska Institutet, Stockholm, Sweden
(author)
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Zierath, Juleen R.Karolinska Institutet,Karolinska Institutet, Stockholm, Sweden
(author)
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Karolinska InstitutetKarolinska Institutet, Stockholm, Sweden
(creator_code:org_t)
Related titles
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In:Journal of Biological Chemistry: American Society for Biochemistry and Molecular Biology, Inc.286:40, s. 34567-345740021-92581083-351X
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