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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
22
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pubmed:dateCreated |
1988-12-30
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pubmed:abstractText |
The antihyperglycemic agent, metformin (dimethylbiguanide), inhibits hepatic gluconeogenesis. To investigate the mechanism involved, glucose production from collagenase-isolated hepatocytes of starved rats was determined after 1 hr incubations with different substrates. In the absence of insulin, glucose production from 10(-2) M lactate-10(-3) M pyruvate, 10(-2)M M alanine, 10(-2) M glutamine and 5 x 10(-3) M glycerol was decreased (35-78%) by high concentrations (10(-2) and 10(-3) M) of metformin. Lower concentrations of metformin were not effective in the absence of insulin, but a therapeutic concentration (10(-5) M) of metformin acted synergistically with insulin (10(-8) M) to suppress gluconeogenesis from each of the substrates by an additional 10-14% compared with insulin (10(-8) M) alone. The synergistic antigluconeogenic effect of metformin (10(-5) M) with insulin (10(-8) M) was achieved without alteration of the contents of NADH and NAD+ in digitonin-separated cytosolic and mitochondrial-rich hepatocyte fractions. Mitochondrial ATP was also unaltered by the metformin (10(-5) M)-insulin (10(-8) M) combination. However, the antigluconeogenic effect of 10(-2) M metformin alone was associated with an increased (by 109%) mitochondrial NADH:NAD+ ratio. Thus reduced gluconeogenesis by high concentrations of metformin (e.g. 10(-2) M) may involve changes of redox state. However, therapeutic concentrations of metformin (e.g. 10(-5) M) potentiate the antigluconeogenic effect of insulin to a similar extent from a range of substrates, without altering energy status or redox state.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Alanine,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Metformin,
http://linkedlifedata.com/resource/pubmed/chemical/NAD
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0006-2952
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
37
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4353-8
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:3058129-Adenosine Triphosphate,
pubmed-meshheading:3058129-Alanine,
pubmed-meshheading:3058129-Animals,
pubmed-meshheading:3058129-Drug Synergism,
pubmed-meshheading:3058129-Gluconeogenesis,
pubmed-meshheading:3058129-Insulin,
pubmed-meshheading:3058129-Liver,
pubmed-meshheading:3058129-Male,
pubmed-meshheading:3058129-Metformin,
pubmed-meshheading:3058129-NAD,
pubmed-meshheading:3058129-Rats,
pubmed-meshheading:3058129-Rats, Inbred Strains
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pubmed:year |
1988
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pubmed:articleTitle |
Inhibition of hepatic gluconeogenesis by metformin. Synergism with insulin.
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pubmed:affiliation |
Department of Pharmaceutical Sciences, Aston University, Birmingham, U.K.
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pubmed:publicationType |
Journal Article
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