Source:http://linkedlifedata.com/resource/pubmed/id/15047617
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2004-3-29
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| pubmed:abstractText |
The bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) was recently identified as a new intracellular binding partner for glucokinase (GK). Therefore, we studied the importance of this interaction for the activity status of GK and glucose metabolism in insulin-producing cells by overexpression of the rat liver and pancreatic islet isoforms of PFK-2/FBPase-2. PFK-2/FBPase-2 overexpression in RINm5F-GK cells significantly increased the GK activity by 78% in cells expressing the islet isoform, by 130% in cells expressing the liver isoform, and by 116% in cells expressing a cAMP-insensitive liver S32A/H258A double mutant isoform. Only in cells overexpressing the wild-type liver PFK-2/FBPase-2 isoform was the increase of GK activity abolished by forskolin, apparently due to the regulatory site for phosphorylation by a cAMP-dependent protein kinase. In cells overexpressing any isoform of the PFK-2/FBPase-2, the increase of the GK enzyme activity was antagonized by treatment with anti-FBPase-2 antibody. Increasing the glucose concentration from 2 to 10 mmol/l had a significant stimulatory effect on the GK activity in RINm5F-GK cells overexpressing any isoform of PFK-2/FBPase-2. The interaction of GK with PFK-2/FBPase-2 takes place at glucose concentrations that are physiologically relevant for the activation of GK and the regulation of glucose-induced insulin secretion. This new mechanism of posttranslational GK regulation may also represent a new site for pharmacotherapeutic intervention in type 2 diabetes treatment.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Glucokinase,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphofructokinase-2,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
0012-1797
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
53
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1020-9
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:15047617-Adenoviridae,
pubmed-meshheading:15047617-Animals,
pubmed-meshheading:15047617-Cell Line,
pubmed-meshheading:15047617-Cloning, Molecular,
pubmed-meshheading:15047617-Forskolin,
pubmed-meshheading:15047617-Genetic Vectors,
pubmed-meshheading:15047617-Glucokinase,
pubmed-meshheading:15047617-Glucose,
pubmed-meshheading:15047617-Humans,
pubmed-meshheading:15047617-Islets of Langerhans,
pubmed-meshheading:15047617-Isoenzymes,
pubmed-meshheading:15047617-Liver,
pubmed-meshheading:15047617-Phosphofructokinase-2,
pubmed-meshheading:15047617-Phosphorylation,
pubmed-meshheading:15047617-Protein Processing, Post-Translational,
pubmed-meshheading:15047617-Rats,
pubmed-meshheading:15047617-Recombinant Proteins,
pubmed-meshheading:15047617-Transfection
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| pubmed:year |
2004
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| pubmed:articleTitle |
Interaction of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) with glucokinase activates glucose phosphorylation and glucose metabolism in insulin-producing cells.
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| pubmed:affiliation |
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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