Source:http://linkedlifedata.com/resource/pubmed/id/11118009
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
2000-12-12
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pubmed:abstractText |
To examine the effect of increased hexosamine flux in liver, the rate-limiting enzyme in hexosamine biosynthesis (glutamine:fructose-6-phosphate amidotransferase [GFA]) was overexpressed in transgenic mice using the PEPCK promoter. Liver from random-fed transgenic mice had 1.6-fold higher GFA activity compared with nontransgenic control littermates (276 +/- 24 pmol x mg(-1) x min(-1) in transgenic mice vs. 176 +/- 18 pmol x mg(-1) x min(-1) in controls, P < 0.05) and higher levels of the hexosamine end product UDP-N-acetyl glucosamine (288 +/- 11 pmol/g in transgenic mice vs. 233 +/- 10 pmol/g in controls, P < 0.001). Younger transgenic mice compared with control mice had lower fasting serum glucose (4.8 +/- 0.5 mmol/l in transgenic mice vs. 6.5 +/- 0.8 mmol/l in controls, P < 0.05) without higher insulin levels (48.0 +/- 7.8 pmol/l in transgenic mice vs. 56.4 +/- 5.4 pmol/l in controls, P = NS); insulin levels were significantly lower in transgenic males (P < 0.05). At 6 months of age, transgenic animals had normal insulin sensitivity by the hyperinsulinemic clamp technique. Hepatic glycogen content was higher in the transgenic mice (108.6 +/- 5.2 pmol/g in transgenic mice vs. 32.8 +/- 1.3 micromol/g in controls, P < 0.01), associated with an inappropriate activation of glycogen synthase. Serum levels of free fatty acids (FFAs) and triglycerides were also elevated (FFAs, 0.67 +/- 0.03 mmol/l in transgenic mice vs. 0.14 +/- 0.01 in controls; triglycerides, 1.34 +/- 0.15 mmol/l in transgenic mice vs. 0.38 +/- 0.01 in controls, P < 0.01). Older transgenic mice became heavier than control mice and exhibited relative glucose intolerance and insulin resistance. The glucose disposal rate at 8 months of age was 154 +/- 5 mg x kg(-1) x min(-1) in transgenic mice vs. 191 +/- 6 mg x kg(-1) x min(-1) in controls (P < 0.05). We conclude that hexosamines are mediators of glucose sensing for the regulation of hepatic glycogen and lipid metabolism. Increased hexosamine flux in the liver signals a shift toward fuel storage, resulting ultimately in obesity and insulin resistance.
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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/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Nonesterified,
http://linkedlifedata.com/resource/pubmed/chemical/Glucosamine,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamine-Fructose-6-Phosphate...,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoenolpyruvate Carboxykinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphorylases,
http://linkedlifedata.com/resource/pubmed/chemical/Triglycerides,
http://linkedlifedata.com/resource/pubmed/chemical/UDP-glucosamine,
http://linkedlifedata.com/resource/pubmed/chemical/Uridine Diphosphate...
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0012-1797
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
49
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2070-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11118009-Adenosine Triphosphate,
pubmed-meshheading:11118009-Animals,
pubmed-meshheading:11118009-Fatty Acids, Nonesterified,
pubmed-meshheading:11118009-Glucosamine,
pubmed-meshheading:11118009-Glucose Intolerance,
pubmed-meshheading:11118009-Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing),
pubmed-meshheading:11118009-Glycogen,
pubmed-meshheading:11118009-Glycogen Synthase,
pubmed-meshheading:11118009-Hyperlipidemias,
pubmed-meshheading:11118009-Liver,
pubmed-meshheading:11118009-Mice,
pubmed-meshheading:11118009-Mice, Inbred C57BL,
pubmed-meshheading:11118009-Mice, Transgenic,
pubmed-meshheading:11118009-Obesity,
pubmed-meshheading:11118009-Phosphoenolpyruvate Carboxykinase (GTP),
pubmed-meshheading:11118009-Phosphorylases,
pubmed-meshheading:11118009-Reference Values,
pubmed-meshheading:11118009-Triglycerides,
pubmed-meshheading:11118009-Uridine Diphosphate N-Acetylgalactosamine
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pubmed:year |
2000
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pubmed:articleTitle |
Overexpression of glutamine: fructose-6-phosphate amidotransferase in the liver of transgenic mice results in enhanced glycogen storage, hyperlipidemia, obesity, and impaired glucose tolerance.
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pubmed:affiliation |
Department of Medicine, University of Utah School of Medicine, Veterans Administration Medical Center, Salt Lake City 84132, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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